Citizendia
Your Ad Here

Prozac, a selective serotonin reuptake inhibitor (SSRI)
Prozac, a selective serotonin reuptake inhibitor (SSRI)
Serotonin-norepinephrine reuptake inhibitor, Venlafaxine
Serotonin-norepinephrine reuptake inhibitor, Venlafaxine

An antidepressant is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia ('milder' depression). Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Psychiatric medication is a licenced Psychoactive drug taken to exert an effect on the Mental state and used to treat Mental disorders Usually utilized Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Dysthymia (pronounced /dɪsˈθaɪmiə/ is a Mood disorder that falls within the depression spectrum. Drug groups known as MAOIs, tricyclics, and SSRIs are particularly associated with the term. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders These medications are now amongst the drugs most commonly prescribed by psychiatrists and as well as other physicians, and their effectiveness and adverse effects are the subject of many studies and competing claims. A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained A psychiatrist (also archaically called an alienist) is a Physician who specializes in Psychiatry and is certified in treating Mental disorders Effectiveness means the capability of producing an Effect. In Physics, an effective theory is similar to a phenomenological theory a framework intended In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery. Nutrients for which there are claims of antidepressant activity include phenylalanine, tyrosine, tryptophan, 5-Hydroxytryptophan, and choline. Phe redirects here For the BitTorrent feature see PHE. For the constellation see Phoenix (constellation. Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an Essential amino acid in the Human diet 5-Hydroxytryptophan or 5-HTP is a naturally-occurring Amino acid, a precursor to the Neurotransmitter Serotonin and an intermediate Choline is an Organic compound, classified as a water-soluble Essential nutrient and usually grouped within the Vitamin B complex

Most antidepressants have a delayed onset of action and are usually taken over the course of weeks, months, or years. They are generally considered distinct from stimulants, and drugs used for an immediate euphoric effect only are not generally considered antidepressants. Stimulant drugs are Drugs that temporarily increase alertness and awareness Happiness is an Emotion associated with feelings ranging from contentment and satisfaction to Bliss and intense Joy. Despite the name, antidepressants are often used in the treatment of other conditions, including anxiety disorders, bipolar disorder, obsessive compulsive disorder, eating disorders, and chronic pain. Anxiety disorder is a blanket term covering several different forms of abnormal pathological anxieties Fears and Phobias In clinical usage "fear" Obsessive-compulsive disorder (OCD is a Chronic Anxiety disorder most commonly characterized by obsessive Distressing Intrusive thoughts An eating disorder is a compulsion to eat or avoid eating that negatively affects both one's physical and mental health Chronic pain is defined as Pain that persists longer than the temporal course of natural healing associated with a particular type of injury or disease process Some have also become known as lifestyle drugs or "mood brighteners". Lifestyle drug is a term commonly applied to medications which treat conditions like Baldness, Impotence, Wrinkles, or Obesity. Other medications not known as antidepressants, including antipsychotics in low doses[1] and benzodiazepines,[2] are also widely used to manage depression. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic

The term antidepressant is sometimes applied to any therapy (e. g. psychotherapy, electro-convulsive therapy, acupuncture) or process (e. Psychotherapy is an Interpersonal, relational intervention used by trained psychotherapists to aid clients in problems of living Electroconvulsive therapy ( ECT) also known as electroshock, is a controversial psychiatric treatment in which Seizures are electrically induced History Antiquity In China, the practice of acupuncture can perhaps be traced as far back as g. sleep disruption, increased light levels, regular exercise) found to improve clinically depressed mood. An inert placebo tends to have a significant antidepressant effect, so establishing something as an antidepressant in a clinical trial involves demonstrating a significant additional effect. Placebo is a substance or procedure a patient accepts as medicine or therapy but which has no specific therapeutic activity In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices

Contents

History

Saint John's Wort
Saint John's Wort

Opium[3] and St John's Wort[4] (as a "nerve tonic") had long been used to alleviate depression, but the contemporary history of antidepressant medications begins with isoniazid. Opium is a Narcotic formed from the Latex (ie sap released by lacerating (or "scoring" the immature seed pods of opium poppies ( St John's wort (pronounced) used alone refers to the species Hypericum perforatum, also known as Tipton's Weed or Klamath weed, but with qualifiers is Isoniazid (also called isonicotinyl hydrazine or INH) is a first-line antituberculous medication used in the prevention and treatment of Tuberculosis

Isoniazid and iproniazid

In 1951, two physicians from the Sea View Hospital on Staten Island, Irving Selikoff and Edward Robitzek, began clinical trials to evaluate two new anti-tuberculosis agents from Hoffman-LaRoche, isoniazid and iproniazid. Tuberculosis (abbreviated as TB for tubercle bacillus or T u' b' erculosis Bacillus --> is a common Isoniazid (also called isonicotinyl hydrazine or INH) is a first-line antituberculous medication used in the prevention and treatment of Tuberculosis Iproniazid ( iproniazid phosphate, marketed under the names Marsilid, Iprozid, Ipronid, Rivivol, Propilniazida) is a monoamine Only the patients with poor prognosis were initially treated; nevertheless, their condition improved dramatically. Prognosis (older Greek πρόγνωσις modern Greek πρόγνωση - literally fore-knowing foreseeing) is a medical term denoting the In addition, Selikoff and Robitzek noted "a subtle general stimulation. . . The patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems. "[5] The promise of the cure for tuberculosis brought by the results of the Sea View Hospital trials was also excitedly discussed in the mainstream press. In 1952, learning of the stimulant-like side effects of the isoniazid, the Cincinnati psychiatrist Max Lurie decided to try it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved the depression in two thirds of their patients and also coined the term antidepressant to describe its action. [6] A similar story happened in Paris, where Jean Delay, the head of psychiatry at Sainte-Anne Hospital, found out from his pulmonology colleagues from Cochin Hospital about the side effects of isoniazid. In Medicine, pulmonology (aka pneumology) is the specialty that deals with Diseases of the Lungs and the Respiratory tract. In 1952, that is even earlier than Lurie and Salzer, Delay with the resident Jean-Francois Buisson also reported the positive action of isoniazid on depressed patients. [7] For the reasons unrelated to the efficacy, isoniazid as antidepressant was soon overshadowed by more toxic iproniazid,[6] although it remains one of the mainstays of the tuberculosis treatment. Active Tuberculosis will kill about two of every three people affected if left untreated The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of diamine oxidase coupled with a weak inhibition of monoamine oxidase A. Amine oxidase is an enzyme involved in the metabolism of Histamine. Monoamine oxidase A is an Isozyme of Monoamine oxidase. It preferentially deaminates Norepinephrine (noradrenaline and serotonin [8]

Another anti-tuberculosis drug tried at the same time by Selikoff and Robitzek, iproniazid, was observed to have a greater "psychostimulant" effect, albeit at the cost of a greater toxicity. Iproniazid ( iproniazid phosphate, marketed under the names Marsilid, Iprozid, Ipronid, Rivivol, Propilniazida) is a monoamine [9] Subsequently to the publications on isoniazid, papers by Jackson Smith, Gordon Kamman, George Crane, and Frank Ayd describing the psychiatric applications of iproniazid also appeared, and Ernst Zeller found iproniazid to be a potent monoamine oxidase inhibitor. Frank Ayd ( October 14, 1920 - March 21, 2008) was an american psychiatrist known for introducing the first Antipsychotic medications Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. [10] Nevertheless, iproniazid had remained relatively obscure until Nathan Kline, the influential and flamboyant head of research at Rockland State Hospital, began its popularization both in medical and popular press as a "psychic energizer". [11][10] While isoniazid was not patentable,[6] Roche put a significant marketing effort behind iproniazid, including promoting its off-label use for depression. Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug's approved label most often concerning the drug's indication. [10] Its sales grew massively in the following years, until it was recalled from the market in 1961 due to the cases of lethal hepatotoxicity. Drug metabolism in liver The human body identifies almost all drugs as foreign substances (i [10]

Imipramine

The discovery that a tricyclic ("three ringed") compound had a significant antidepressant effect was also first made in the early 1950s, by Roland Kuhn in a Swiss psychiatric hospital. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s By that time antihistamine derivatives were coming in to use to treat surgical shock and then as psychiatric neuroleptics. A histamine antagonist is an agent which serves to inhibit the release or action of Histamine. Although, in 1955, reserpine was indicated to be more effective than placebo in alleviating anxious depression, neuroleptics (literally "to seize the neuron") were developing for use as sedatives and antipsychotics. Reserpine is an Indole Alkaloid Antipsychotic and Antihypertensive drug that has been used for the control of high blood pressure A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia.

In attempting to improve the effectiveness of one of them, chlorpromazine, in conjunction with the Geigy pharmaceutical company, Kuhn discovered that compound "G 22355" (manufactured and patented in the US in 1951 by Häfliger and Schinder) had a beneficial effect in patients with depression with mental and motor retardation. Chlorpromazine (as chlorpromazine Hydrochloride, abbreviated CPZ, marketed in the US as Thorazine) is a Phenothiazine Antipsychotic Novartis International AG is a multinational Pharmaceutical company based in Basel Switzerland that manufactures drugs such as Clozapine [12] He first reported his findings on what he called a "thymoleptic" (literally "taking hold of the emotions", by contrast with neuroleptics, "taking hold of the nerves") in 1955/56 and they gradually became established, resulting in the marketing of the first tricyclic antidepressant, imipramine, soon followed by variants. Imipramine (sold as Antideprin, Deprenil, Deprimin, Deprinol, Depsonil, Dynaprin, Eupramin, Imipramil

Later history

These new drug therapies became prescription-only medications in the 1950s. It was estimated that no more than 50 to 100 people per million suffered from the kind of depression that these new drugs would treat and pharmaceutical companies were not enthusiastic. Sales through the 1960s remained poor compared to the major tranquilizers (neuroleptics/antipsychotics) and minor tranquilizers (such as benzodiazepines), which were being marketed for different uses. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic

The term antidepressant is reported to have been coined by Lurie and to not have been widely adopted until at least the 1960s. [13] Imipramine remained in common use and numerous successors were introduced. The field of MAO inhibitors remained quiet for many years until "reversible" forms affecting only the MAO-A subtype were introduced, avoiding some of the adverse effects. [14][15][16]

Most pharmacologists by the 1960s thought the main therapeutic action of tricyclics was to inhibit norepinephrine reuptake, but it was gradually observed that this action was associated with energizing and motor stimulating effects whilst some antidepressant compounds appeared to have differing effects through action on serotonin systems (notably proposed by Carlsson and Lindqvist (1969) and Lapin and Oxenkrug (1969)). Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons

Researchers began a process of rational drug design to isolate antihistamine-derived compounds that would 'selectively' (specifically) target these systems. Drug design is the approach of finding drugs by design based on their Biological targets Typically a drug target is a key Molecule involved in a particular The first such compound to be patented, in 1971, was zimelidine, whilst the first released clinically was indalpine. Zimelidine ( Normud, Zelmid) was the first Selective serotonin reuptake inhibitor (SSRI Antidepressant to be marketed Indalpine is a Serotonin uptake inhibitor. Fluoxetine (Prozac), FDA approved for commercial use in 1988, became the first blockbuster SSRI. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Fluoxetine was developed at Eli Lilly in the early 1970s by Bryan Molloy, David Wong and others. [17][18]

While it had fallen out of favor in most countries through the 19th and 20th centuries, the herb St John's Wort had become increasingly popular in Germany where Hypericum extracts eventually became licensed, packaged and prescribed by doctors. St John's wort (pronounced) used alone refers to the species Hypericum perforatum, also known as Tipton's Weed or Klamath weed, but with qualifiers is Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. Hypericum is a Genus of about 400 Species of Flowering plants in the family Clusiaceae, Subfamily Hypericoideae Small-scale efficacy trials were carried out from the 1970s and 1980s, and attention grew in the 1990s following a meta-analysis of these. In Statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses [19] It remained an over-the-counter drug (OTC) or supplement in most countries and research continued to investigate its neurotransmitter effects and active components, particularly hyperforin[20][21]

SSRIs became known as "novel antidepressants" along with other newer drugs such as SNRIs and NRIs with various different selective effects, such as venlafaxine, duloxetine, nefazodone and mirtazapine[22]

Types of Antidepressants

Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are a family of antidepressants considered to be the current standard of drug treatment. Over-the-counter (OTC drugs are medicines that may be sold without a prescription, in contrast to Prescription drugs The name "over-the-counter" Hyperforin is one of the principal constituents identified in St John's wort. Norepinephrine reuptake inhibitors ( NRIs) also known as noradrenaline reuptake inhibitors ( NARIs) are compounds that elevate the extracellular level of Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 Duloxetine (brand names Cymbalta, Yentreve) is a Serotonin-norepinephrine reuptake inhibitor (SNRI used for Major depressive disorder (MDD Nefazodone hydrochloride (trade name Serzone, Nefadar) is an Antidepressant drug marketed by Bristol-Myers Squibb. Mirtazapine is an Antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders It is thought that one cause of depression is an inadequate amount of serotonin, a chemical used in the brain to transmit signals between neurons. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons SSRIs are said to work by preventing the reuptake of serotonin (also known as 5-hydroxytryptamine, or 5-HT) by the presynaptic neuron, thus maintaining higher levels of 5-HT in the synapse.

This family of drugs includes fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro, Esipram), citalopram (Celexa), and sertraline (Zoloft). Paroxetine (trade names Seroxat, Paxil, Parotin, Aropax, Xetanor, ParoMerck, Rexetin) is a Selective serotonin Escitalopram (trade names Lexapro, Cipralex) is the pure (S Enantiomer of Citalopram and is a Selective serotonin reuptake inhibitor Citalopram is an Antidepressant drug used to treat major depression associated with Mood disorders It is also used on occasion in the treatment These antidepressants typically have fewer adverse events and side effects than the tricyclics or the MAOIs, although such effects as drowsiness, dry mouth, nervousness, anxiety, insomnia, decreased appetite, and decreased ability to function sexually may occur. Some side effects may decrease as a person adjusts to the drug, but other side effects may be persistent. Though safer than first generation antidepressants, SSRIs may not work on as many patients are previous classes of antidepressants, suggesting the role of norepinephrine in depression is still important.

Recently, work by two researchers has called into question the link between serotonin deficiency and symptoms of depression, noting that the efficacy of SSRIs as treatment does not in itself prove the link. [23] Recent research indicates that these drugs may interact with transcription factors known as "clock genes,"[24] which may play a role in the addictive properties of drugs (drug abuse), and possibly in obesity. [25][26]

Recent randomized controlled trials published in the Archives of General Psychiatry showed that up to one-third of the effect of SSRI Treatment can be seen in the first week. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare These early effects have also been shown to have a secondary effect of increasing the absolute reduction in HDRS scores by 50%. Even more recent studies, published in the Archives of General Psychiatry, found that 25% of so-called clinical depression does not meet the disease criteria for the disease and could be considered to be ordinary sadness and adjustment to the difficulties in life.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta) are a newer form of antidepressant that works on both norepinephrine and 5-HT. Serotonin-norepinephrine reuptake inhibitors (SNRIs are a class of Antidepressant used in the treatment of major depression and other mood disorders Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 Duloxetine (brand names Cymbalta, Yentreve) is a Serotonin-norepinephrine reuptake inhibitor (SNRI used for Major depressive disorder (MDD They typically have similar side effects to the SSRIs, although there may be a withdrawal syndrome on discontinuation that may necessitate dosage tapering.

Noradrenergic and specific serotonergic antidepressants (NASSAs)

Noradrenergic and specific serotonergic antidepressants (NASSAs) form a newer class of antidepressants which purportedly work to increase norepinephrine (noradrenaline) and serotonin neurotransmission by blocking presynaptic alpha-2 adrenergic receptors while at the same time minimizing serotonin related side-effects by blocking certain serotonin receptors. Noradrenergic and selective serotonergic antidepressants (abbreviated NaSSAs) are a relatively new class of Antidepressants They are thought to work by blocking presynaptic Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors The only example of this class in clinical use is mirtazapine (Avanza, Zispin, Remeron). Mirtazapine is an Antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression.

Norepinephrine (noradrenaline) reuptake inhibitors (NRIs)

Norepinephrine (noradrenaline) reuptake inhibitors (NRIs) such as reboxetine (Edronax) act via norepinephrine (also known as noradrenaline). Norepinephrine reuptake inhibitors ( NRIs) also known as noradrenaline reuptake inhibitors ( NARIs) are compounds that elevate the extracellular level of Reboxetine is an Antidepressant drug used in the treatment of Clinical depression, Panic disorder and ADD/ADHD, developed by Pharmacia (now NRIs are thought to have a positive effect on concentration and motivation in particular.

Norepinephrine-dopamine reuptake inhibitors

Norepinephrine-dopamine reuptake inhibitors such as bupropion (Wellbutrin, Zyban) inhibit the neuronal reuptake of dopamine and norepinephrine (noradrenaline). A Norepinephrine-dopamine reuptake inhibitor is a class of drugs that is both Dopamine reuptake inhibitor Norepinephrine reuptake inhibitor Bupropion ( INN, previously known as amfebutamone; sold as Wellbutrin, Zyban, and several other Trade names is an atypical Antidepressant Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a [27]

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants are the oldest class of antidepressant drugs and include such medications as amitriptyline and desipramine. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s Amitriptyline (or Amitryptyline) hydrochloride (sold as Elavil Tryptanol Endep Elatrol Tryptizol Trepiline Laroxyl Saroten is a Tricyclic antidepressant Desipramine is a Tricyclic antidepressant (TCA that inhibits the reuptake of Norepinephrine. Tricyclics block the reuptake of certain neurotransmitters such as norepinephrine (noradrenaline) and serotonin. They are used less commonly now due to the development of more selective and safer drugs. Side effects include increased heart rate, drowsiness, dry mouth, constipation, urinary retention, blurred vision, dizziness, confusion, and sexual dysfunction. The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic Toxicity occurs at approximately ten times normal dosages. However, tricyclic antidepressants are still used because of their high potency, especially in severe cases of clinical depression.

Monoamine oxidase inhibitor (MAOIs)

Monoamine oxidase inhibitors (MAOIs) such as phenelzine (Nardil) may be used if other antidepressant medications are ineffective. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Phenelzine (sold as Nardil) is a Monoamine oxidase inhibitor (MAOI used as an Antidepressant drug. Because there are potentially fatal interactions between this class of medication and certain foods (particularly those containing Tyramine), as well as certain drugs, classic MAOIs are rarely prescribed anymore. In organic Chemistry tyramine (4-hydroxy- Phenethylamine, para-tyramine p-tyramine is a Monoamine compound derived from the MAOIs work by blocking the enzyme monoamine oxidase which breaks down the neurotransmitters dopamine, serotonin, and norepinephrine (noradrenaline). MAOIs can be as effective as tricyclic antidepressants, although they can have a higher incidence of dangerous side effects (as a result of inhibition of cytochrome P450 in the liver). A new generation of MAOIs has been introduced; moclobemide (Manerix), known as a reversible inhibitor of monoamine oxidase A (RIMA), acts in a more short-lived and selective manner and does not require a special diet. Moclobemide (sold as Aurox, Manerix) is a drug primarily used to treat depression and Social anxiety. RIMA redirects here For the Régiments d'Infanterie de Marine of the French Army see Troupes de marine Reversible inhibitors of monoamine oxidase type-A ( Additionally, (selegiline) marketed as Emsam in a transdermal form is not a classic MAOI in that at moderate dosages it tends to effect MAO-B which does not require any dietary restrictions. Selegiline (l-deprenyl Eldepryl Zelapar or Anipryl Veterinary) is a drug used for the treatment of early-stage Parkinson's disease, Depression Emsam (selegiline transdermal system is a Transdermal patch using the Monoamine oxidase inhibitor (MAOI Selegiline.

Augmenter drugs

Some antidepressants have been found to work more effectively in some patients when used in combination with another drug. Such "augmenter" drugs include tryptophan (Tryptan) and buspirone (Buspar). Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an Essential amino acid in the Human diet Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol,

Tranquillizers and sedatives, typically the benzodiazepines, may be prescribed to ease anxiety and promote sleep. A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness A sedative, or more specifically a sedative-hypnotic, is a substance that depresses the Central nervous system (CNS resulting in calmness relaxation sleepiness Because of their high potential for fostering dependence, these medications are intended only for short-term or occasional use. Medications often are used not for their primary function but to exploit what are normally side effects. In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery. Quetiapine fumarate (Seroquel) is designed primarily to treat schizophrenia and bipolar disorder, but a frequently reported side-effect is somnolence. Quetiapine ( kwe-TYE-a-peen marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, is an Atypical antipsychotic Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c Therefore, this drug can be used in place of an antianxiety agent such as clonazepam (Klonopin, Rivotril). Clonazepam (marketed by Roche under the trade-names Klonopin in the United States and Rivotril, Ravotril or Rivatril in Europe South

Antipsychotics such as risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel) are prescribed as mood stabilizers and are also effective in treating anxiety. Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the Netherlands, United States, Canada, the Olanzapine ( Zyprexa, Zyprexa Zydis, Zalasta, Zolafren, Olzapin, or in combination with Fluoxetine Symbyax) is Quetiapine ( kwe-TYE-a-peen marketed by AstraZeneca as Seroquel and by Orion Pharma as Ketipinor, is an Atypical antipsychotic Their use as mood stabilizers is a recent phenomenon and is controversial with some patients. Antipsychotics (typical or atypical) may also be prescribed in an attempt to augment an antidepressant, to make antidepressant blood concentration higher, or to relieve psychotic or paranoid symptoms often accompanying clinical depression. Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic Paranoia is a disturbed thought process characterized by excessive Anxiety or Fear, often to the point of Irrationality and Delusion. However, they may have serious side effects, particularly at high dosages, which may include blurred vision, muscle spasms, restlessness, tardive dyskinesia, and weight gain. In Psychology, visual perception is the ability to interpret information from Visible light reaching the Eyes The resulting Perception is also Tardive dyskinesia is a variety of dyskinesia (involuntary repetitive movements manifesting as a side effect of long-term or high-dose use of Dopamine antagonists

Antidepressants by their nature behave similarly to psychostimulants. Antianxiety medications by their nature are depressants. Close medical supervision is critical to proper treatment if a patient presents with both illnesses because the medications tend to work against each other.

Psycho-stimulants are sometimes added to an antidepressant regimen if the patient suffers from anhedonia, hypersomnia and/or excessive eating as well as low motivation. In Psychology, anhedonia ( Greek αν- an- without + ηδονή hēdonē pleasure) is an inability to experience Hypersomnia is excessive amount of sleepiness. Description Hypersomnia is characterized by reoccuring episodes of Excessive daytime sleepiness These symptoms which are common in atypical depression can be quickly resolved with the addition of low to moderate dosages of amphetamine or methylphenidate (brand names Adderall and Ritalin, respectively) as these chemicals enhance motivation and social behavior, as well as suppress appetite and sleep. Atypical Depression (AD is a subtype of Dysthymia and Major Depression characterized by mood reactivity — being able to experience improved mood in response to positive events Adderall is a brand-name pharmaceutical Psychostimulant composed of mixed Amphetamine salts, the actions of which are Sympathomimetic These chemicals are also known to restore sex drive. Extreme caution must be used however with certain populations. Stimulants are known to trigger manic episodes in people suffering from bipolar disorder. They are also easily abused as they are effective substitutes for Methamphetamine when used recreationally. Close supervision of those with substance abuse disorders is urged. Emotionally labile patients should avoid stimulants, as they exacerbate mood shifting.

Lithium remains the standard treatment for bipolar disorder and is often used in conjunction with other medications, depending on whether mania or depression is being treated. Lithium in pharmacology refers to use of the Lithium Ion, Li+ as a drug Lithium's potential side effects include thirst, tremors, light-headedness, and nausea or diarrhea. Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Some of the anticonvulsants, such as carbamazepine (Tegretol), sodium valproate (Epilim), and lamotrigine (Lamictal), are also used as mood stabilizers, particularly in bipolar disorder. The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Carbamazepine ("CBZ" is an Anticonvulsant and mood stabilizing drug used primarily in the treatment of Epilepsy and Bipolar disorder See also Valproic acid Sodium valproate ( INN) or valproate sodium ( USAN) is the sodium salt of Valproic acid and is an Lamotrigine (marketed as Lamictal (ləˈmɪktəl by GlaxoSmithKline, called Lamictin in South Africa, he למוג'ין ( Lamogine

Prescription trends

In the United Kingdom the use of antidepressants increased by 234% in the 10 years up to 2002. [28] In the United States a 2005 independent report stated that 11% of women and 5% of men in the non-institutionalized population (2002) take antidepressants[29] A 1998 survey found that 67% of patients diagnosed with depression were prescribed an antidepressant. [30] A 2007 study purports that 25% of Americans were overdiagnosed with depression, regardless of any medical intervention. [31] The findings were based on a national survey of 8,098 people.

A 2002 survey found that about 3. 5% of all people in France were being prescribed antidepressants, compared to 1. This article is about the country For a topic outline on this subject see List of basic France topics. 7% in 1992, often for conditions other than depression and often not in line with authorizations or guidelines[32] Between 1996 and 2004 in British Columbia, antidepressant use increased from 3. British Columbia (ˌbrɪtɨʃ kəˈlʌmbiə ( BC) ( (la Colombie-Britannique C 4% to 7. 2% of the population[33] Data from 1992 to 2001 from the Netherlands indicated an increasing rate of prescriptions of SSRIs, and an increasing duration of treatment. The Netherlands ( Dutch:, ˈnedərlɑnt is the European part of the Kingdom of the Netherlands, which consists of the Netherlands the Netherlands [34]

Surveys indicate that antidepressant use, particularly of SSRIs, has increased rapidly in most developed countries, driven by an increased awareness of depression together with the availability and commercial promotion of new antidepressants. [35] Antidepressants are also increasingly used worldwide for non-depressive patients as studies continue to show the potential of immunomodulatory, analgesic and anti-inflammatory properties in antidepressants.

The choice of particular antidepressant is reported to be based, in the absence of research evidence of differences in efficacy, on seeking to avoid certain side effects, and taking into account comorbid (co-occurring) psychiatric disorders, specific clinical symptoms and prior treatment history[36]

It is also reported that, despite equivocal evidence of a significant difference in efficacy between older and newer antidepressants, clinicians perceive the newer drugs, including SSRIs and SNRIs, to be more effective than the older drugs (tricyclics and MAOIs). [37] A survey in the UK found that male general physicians were more likely to prescribe antidepressants than female doctors. [38]

Most commonly prescribed antidepressants

Structural formula of the SSRI escitalopram, in its free base form.
Structural formula of the SSRI escitalopram, in its free base form. Escitalopram (trade names Lexapro, Cipralex) is the pure (S Enantiomer of Citalopram and is a Selective serotonin reuptake inhibitor

The most commonly prescribed antidepressants in the US retail market in 2006 [39] were:

The most commonly prescribed antidepressant in Germany is reported to be (concentrated extracts of) hypericum perforatum (St John's Wort). St John's wort (pronounced) used alone refers to the species Hypericum perforatum, also known as Tipton's Weed or Klamath weed, but with qualifiers is [13] In the Netherlands, paroxetine, marketed as Seroxat among generic preparations, is the most prescribed antidepressant, followed by the tricyclic antidepressant amitriptyline, citalopram and venlafaxine. [14]

Mechanisms of action

The therapeutic effects of antidepressants are believed to be related to their effects on neurotransmitters. See Chemical synapse for an introduction to concepts and terminology used in this article Monoamine oxidase inhibitors (MAOIs) block the break-down of monoamine neurotransmitters (serotonin and norepinephrine) by inhibiting the enzymes which oxidize them, thus leaving higher levels still active in the brain (synaptic cleft). Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands

Tricyclic antidepressants (TCAs) prevent the reuptake of various neurotransmitters, including serotonin, norepinephrine, and dopamine. See Chemical synapse for an introduction to concepts and terminology used in this article Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Selective serotonin reuptake inhibitors (SSRIs) more specifically prevent the reuptake of serotonin (thereby increasing the level of active serotonin in synapses of the brain). Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain Other novel antidepressants specifically affect serotonin and other neurotransmitters.

A theory centered on neurotransmitter effects appears to be incomplete, however. Neurotransmitter levels are altered as soon as the antidepressant chemicals build up in the bloodstream, but effects on mood appear to occur several days or weeks later.

One explanation of this holds that the "down-regulation" of neurotransmitter receptors—an apparent consequence of excess signaling and a process that takes several weeks—is actually the mechanism responsible for the alleviation of depressive symptoms. WikipediaWikipedia is not a dictionary ---> Downregulation is the process by which Transmembrane receptors are Integral membrane proteins which reside and operate typically within a cell's Plasma membrane, but also in the membranes of Another hypothesis is that antidepressants may have some longer-term effects due to the promotion of neurogenesis in the hippocampus, an effect found in mice[40][41] Other animal research suggests that antidepressants can also affect the expression of genes in brain cells, by influencing "clock genes". Neurogenesis ( birth of Neurons ' is the process by which neurons are created The hippocampus is a part of the Forebrain, located in the medial Temporal lobe. [42]

Other research suggests that delayed onset of clinical effects from antidepressants indicates involvement of adaptive changes in antidepressant effects. Rodent studies have consistently shown upregulation of the 3, 5-cyclic adenosine monophosphate (cAMP) system induced by different types of chronic but not acute antidepressant treatment including serotonin and norepinephrine uptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, lithium and electroconvulsions. Cyclic adenosine monophosphate ( cAMP, cyclic AMP or 3'-5'-cyclic Adenosine monophosphate) is a Second messenger that is important in many biological cAMP is synthesized from adenosine 5-triphosphate (ATP) by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy A phosphodiesterase is any Enzyme that breaks a Phosphodiester bond. [43] Data also suggest antidepressants to have the ability of modulating neural plasticity in longterm administration. Neuroplasticity (variously referred to as brain plasticity, cortical plasticity or cortical re-mapping) refers to the changes that occur in [44]

One theory regarding the cause of depression is that it is characterized by an overactive hypothalamic-pituitary-adrenal axis (HPA axis) that resembles the neuro-endocrine response to stress. The hypothalamic-pituitary-adrenal axis ( HPA or HTPA axis) also known as the Limbic -hypothalamic-pituitary-adrenal axis (LHPA axis is a complex set of direct influences These HPA axis abnormalities participate in the development of depressive symptoms, and antidepressants serve to regulate HPA axis function. [45]

Anti-inflammatory and immunomodulation

Recent studies show pro-inflammatory cytokine processes take place during depression, mania and bipolar disease, and is possible that symptoms manifest in these psychiatric illnesses are being attenuated by pharmacological affect of antidepressants on the immune system. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition [46][47][48][49][50]

Studies also show that the chronic secretion of stress hormones as a result of disease, including somatic infections or autoimmune syndromes may reduce the effect of neurotransmitters or other receptors in the brain by cell-mediated pro-inflammatory pathways, thereby leading to the dysregulation of neurohormones. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body "Somatic" redirects here for the musician known as Somatic see Hahn Rowe. An infection is the detrimental Colonization of a host Organism by a foreign Species. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues See Chemical synapse for an introduction to concepts and terminology used in this article Cell-mediated immunity is an Immune response that does not involve Antibodies or complement but rather involves the activation of Macrophages [51] SSRIs, SNRIs and tricyclic antidepressants acting on serotonin, norepinephrine and dopamine receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of Interferon-gamma (IFN-gamma) and Interleukin-10 (IL-10), as well as TNF-alpha and Interleukin-6 (IL-6). Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons Norepinephrine ( INN) (abbreviated norepi or NE) or noradrenaline ( BAN) (abbreviated NA or NAd) is a Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Interferon-gamma ( IFN-γ) is a Dimerized soluble Cytokine that is the only member of the type II class of Interferons This interferon was originally Interleukin -10 (IL-10 or IL10 also known as human cytokine synthesis inhibitory factor (CSIF is an anti- Inflammatory Cytokine. Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic Antidepressants have also been shown to suppress TH1 upregulation. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or [52][53][54][55][56]

Antidepressants, specifically TCAs and dual serotonergic-noradrenergic reuptake inhibition by dual SNRIs (or SSRI-NRI combinations), have also shown analgesic properties. [57][58]

These studies warrant investigation for antidepressants for use in both psychiatric and non-psychiatric illness and that a psycho-neuroimmunological approach may be required for optimal pharmacotherapy. Psychoneuroimmunology (PNI is the study of the interaction between psychological processes and the nervous and immune systems of the human body Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease [59] Future antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines. [60]

Therapeutic efficacy

There is a large amount of research evaluating the potential therapeutic effects of antidepressants, whether through efficacy studies under experimental conditions (including randomized clinical trials) or through studies of "real world" effectiveness. A sufficient response to a drug is often defined as at least a 50% reduction in self-reported or observed symptoms, with a partial response often defined as at least a 25% reduction. The term remission indicates a virtual elimination of depression symptoms, albeit with the risk of a recurrence of symptoms or complete relapse. Full remission or recovery signifies a full sustained return to a "normal" psychological state with full functioning.

Review studies

Recent clinical reviews include:

Clinical guidelines

The American Psychiatric Association 2000 Practice Guideline for the Treatment of Patients with Major Depressive Disorder [71] indicates that, if preferred by the patient, antidepressant medications may be provided as an initial primary treatment for mild major depressive disorder; antidepressant medications should be provided for moderate to severe major depressive disorder unless electroconvulsive therapy is planned; and a combination of antipsychotic and antidepressant medications or electroconvulsive therapy should be used for psychotic depression. The American Psychiatric Association (APA is the main Professional organization of Psychiatrists and trainee psychiatrists in the United States, and the Electroconvulsive therapy ( ECT) also known as electroshock, is a controversial psychiatric treatment in which Seizures are electrically induced It states that efficacy is generally comparable between classes and within classes and that the initial selection will largely be based on the anticipated side effects for an individual patient, patient preference, quantity and quality of clinical trial data regarding the medication, and its cost.

The UK National Institute for Clinical Excellence (NICE) 2004 guidelines indicate that antidepressants should not be used for the initial treatment of mild depression, because the risk-benefit ratio is poor; that for moderate or severe depression an SSRI is more likely to be tolerated than a tricyclic; and that antidepressants for severe depression should be combined with a psychological treatment such as Cognitive Behavioural Therapy. See also Cognitive Therapy Cognitive Behavioral Therapy ( CBT) is an umbrella-term for psychotherapeutic systems that deal with cognitions interpretations [72]

Efficacy limitations and strategies

Between 30% and 50% of individuals treated with a given antidepressant do not show a response. [73][74] Even where there has been a robust response, significant continuing depression and dysfunction is common, with relapse rates 3 to 6 times higher in such cases. [75] In addition, antidepressant drugs tend to lose efficacy over the course of treatment[76] A number of strategies are used in clinical practice to try to overcome these limits and variations. [77]

"Trial and error" switching

The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved following six to eight weeks of treatment with an antidepressant, to switch to an antidepressant in the same class, then to a different class of antidepressant. The American Psychiatric Association (APA is the main Professional organization of Psychiatrists and trainee psychiatrists in the United States, and the

A recent meta-analysis review found wide variation in the findings of prior studies; for patients who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug, with between 5% and 39% ending treatment due to adverse effects. The more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial. [74]

Augmentation and combination

For a partial response, the American Psychiatric Association guidelines advise adding a different kind of pharmaceutical agent to the antidepressant. Studies suggest that most patients fail to achieve remission on a given antidepressant, and augmentation strategies used in clinical practice include the use of lithium and thyroid augmentation, but there is not a good evidence base for these practices or for more novel strategies such as the use of selective dopamine agonists, sex steroids, NRI's, glucocorticoid-specific agents, or the newer anticonvulsants[78]

A combination strategy involves adding one or more additional antidepressants, usually from different classes so as to have a diverse neurochemical effect. Lithium (ˈlɪθiəm is a Chemical element with the symbol Li and Atomic number 3 The thyroid is one of the largest Endocrine glands in the body A dopamine agonist is a compound that activates Dopamine receptors mimicking the effect of the neurotransmitter Dopamine. Sex steroids, also known as gonadal steroids, are Steroid hormones that interact with Vertebrate Androgen or Estrogen receptors Norepinephrine reuptake inhibitors ( NRIs) also known as noradrenaline reuptake inhibitors ( NARIs) are compounds that elevate the extracellular level of Glucocorticoids (GC are a class of Steroid hormones characterised by an ability to bind with the glucocorticoid receptor ( GR) and trigger similar effects The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy. [79]

Long-term use

The therapeutic effects of antidepressants typically do not continue once the course of medication ends, resulting in a high rate of relapse. A recent meta-analysis of 31 placebo-controlled antidepressant trials, mostly limited to studies covering a period of one year, found that 18% of patients who had responded to an antidepressant relapsed while still taking it, compared to 41% whose antidepressant was switched for a placebo. [80] The American Psychiatric Association guidelines advise four to five months of continuation treatment on an antidepressant following the resolution of symptoms. For patients with a history of depressive episodes, the British Association for Psychopharmacology's 2000 Guidelines for Treating Depressive Disorders with Antidepressants advise remaining on an antidepressant for at least six months and as long as five years or indefinitely.

Whether or not someone relapses after stopping an antidepressant does not appear to be related to the duration of prior treatment, however, and gradual loss of therapeutic benefit during the course also occurs. A strategy involving the use of pharmacotherapy in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies. [81][82]

Medication failure

Approximately 30% of patients have remission of depression with medications. [83] For patients with inadequate response, either adding sustained-release bupropion (initially 200 mg per day then increase by 100 mg up to total of 400 mg per day) or buspirone (up to 60 mg per day) for augmentation as a second drug can cause remission in approximately 30% of patients,[84] while switching medications can achieve remission in about 25% of patients. Bupropion ( INN, previously known as amfebutamone; sold as Wellbutrin, Zyban, and several other Trade names is an atypical Antidepressant Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, [85]

By pregnancy

There is uncertainty whether pregnancy contributes to medication failure, because the only report so far has drawn much controversy on itself:

In 2006, a widely reported study published in the Journal of the American Medical Association (JAMA) challenged the common assumption that hormonal changes during pregnancy protected expectant mothers against depression, finding that discontinuing anti-depressive medication during pregnancy led to more frequent relapse. JAMA The Journal of the American Medical Association is an international peer-reviewed general Medical journal, published 48 times per year by the American [86] The JAMA article did not disclose that several authors had financial ties to pharmaceutical companies making antidepressants. The JAMA later published a correction noting the ties[87] and the authors maintain that the ties have no bearing on their research work. Obstetrician and perinatologist Adam Urato told the Wall Street Journal that patients and medical professionals need advice free of industry influence. [88]

Tolerance and dependence

Most antidepressants, including the SSRIs and tricyclics, are known to produce tolerance (i. Drug tolerance occurs when a subject's reaction to a Psychoactive drug (such as a painkiller or intoxicant decreases so that larger doses are required to achieve the same effect e. a decrease in the effects of a drug over time), and withdrawal (particularly if abrupt) may produce adverse effects, which can range from mild to extremely severe. Withdrawal, also known as withdrawal/abstinence syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes Physical dependence is

Antidepressants do not seem to have all of the same addictive qualities as other substances such as nicotine, caffeine, cocaine, or other stimulants - in other words, while antidepressants may cause dependence and withdrawal they do not seem to cause uncontrollable urges to increase the dose due to euphoria or pleasure, and thus do not meet the strict definition of an addictive substance. The term " addiction " is used in many contexts to describe an obsession compulsion or excessive Physical dependence or psychological dependence such as Nicotine is an Alkaloid found in the Nightshade family of plants ( Solanaceae) which constitutes approximately 0 Caffeine is a bitter white crystalline Xanthine Alkaloid that acts as a Psychoactive Stimulant Drug and a mild Diuretic Cocaine ( benzoylmethyl ecgonine) is a Crystalline Tropane Alkaloid that is obtained from the leaves of the Coca plant Stimulant drugs are Drugs that temporarily increase alertness and awareness Euphoria is a medically recognized emotional state related to Pleasure and Happiness. Pleasure is commonly conceptualized as a positive experience Happiness, Entertainment, Enjoyment, ecstasy, and euphoria, but is hard However, antidepressants do meet the World Health Organisation definition of "dependency-inducing", and indeed the SSRIs are listed by the organisation as among the most strongly dependency-inducing substances in existence.

If an SSRI medication is suddenly discontinued, it may produce both somatic and psychological withdrawal symptoms, a phenomenon known as "SSRI discontinuation syndrome" (Tamam & Ozpoyraz, 2002). Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Withdrawal, also known as withdrawal/abstinence syndrome, refers to the characteristic signs and symptoms that appear when a drug that causes Physical dependence is The term " addiction " is used in many contexts to describe an obsession compulsion or excessive Physical dependence or psychological dependence such as SSRI discontinuation syndrome, also known as SSRI withdrawal syndrome or SSRI cessation syndrome is a Withdrawal syndrome that can occur during or following the interruption When the decision is made to stop taking antidepressants it is common practice to "wean" off of them by slowly decreasing the dose over a period of several weeks or months, although often this will reduce the severity of the discontinuation reaction, rather than prevent it. Most cases of discontinuation syndrome last between one and four weeks, though there are examples of patients (especially those who have used the drugs for longer periods of time, or at a higher dose) experiencing adverse effects such as impaired concentration, poor short-term memory, elevated anxiety and sexual dysfunction, for months or even years after discontinuation.

It is generally not a good idea to take antidepressants without a prescription. The selection of an antidepressant and dosage suitable for a certain case and a certain person is a lengthy and complicated process, requiring the knowledge of a professional. Certain antidepressants can initially make depression worse, can induce anxiety, or can make a patient aggressive, dysphoric or acutely suicidal. Anxiety is a physiological and psychological state characterized by Cognitive, Somatic, Emotional and Behavioral components A suicide crisis, suicidal crisis, or potential suicide, is a situation in which a person is attempting to kill him or herself or is seriously contemplating In certain cases, an antidepressant can induce a switch from depression to mania or hypomania, can accelerate and shorten a manic cycle (i. Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition This article is an expansion of a section entitled '''Hypomania''' from within the main article Bipolar disorder. e. promote a rapid-cycling pattern), or can induce the development of psychosis (or just the re-activation of latent psychosis) in a patient with depression who was not psychotic before the antidepressant. Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic

Side effects

Antidepressants can often cause side effects, and an inability to tolerate these is the most common cause of discontinuing an otherwise working medication. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences

Side effects of SSRIs: Nausea, diarrhea, headaches. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted Sexual side effects are also common with SSRIs, such as loss of libido, failure to reach orgasm and erectile problems. Libido in its common usage means Sexual desire however more technical definitions such as those found in the work of Carl Jung, are more general referring to libido An orgasm (sexual climax is the conclusion of the plateau phase of the sexual response cycle, and may be experienced by both males and females Serotonin syndrome is also a worrying condition associated with the use of SSRIs. Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use inadvertent interactions between drugs or the recreational The Food and Drug Administration has included Black Box warnings on all SSRIs stating how they double suicidality (from 2 in 1,000 to 4 in 1,000) in children and adolescents who are prescribed these drugs. [89]

Side effects of TCAs (tricyclic antidepressants): Fairly common side effects include dry mouth, blurred vision, drowsiness, dizziness, tremors, sexual problems, skin rash, and weight gain or loss. Xerostomia is the medical term for a dry mouth due to a lack of Saliva. Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c Many different terms are often used to describe what is collectively known as dizziness. A rash is a change of the Skin which affects its color appearance or Texture.

Side effects of MAOIs (monoamine oxidase inhibitors): Rare side effects of MAOIs like phenelzine (brand name: Nardil) and tranylcypromine (brand name: Parnate) include liver inflammation, heart attack, stroke, and seizures. Phenelzine (sold as Nardil) is a Monoamine oxidase inhibitor (MAOI used as an Antidepressant drug. Tranylcypromine (sold under the brand name Parnate) is a Monoamine oxidase inhibitor (MAOI used as an Antidepressant drug. Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Serotonin syndrome is a side effect of MAOIs and SSRIs when they are combined. Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use inadvertent interactions between drugs or the recreational

General

Although recent drugs may have fewer side effects, patients sometimes report severe side effects associated with their discontinuation, particularly with paroxetine and venlafaxine. Paroxetine (trade names Seroxat, Paxil, Parotin, Aropax, Xetanor, ParoMerck, Rexetin) is a Selective serotonin Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 Additionally, a certain percentage of patients do not respond to antidepressant drugs. Another advantage of some newer antidepressants is they can show effects within as few as five days, whereas most take four to six weeks to show a change in mood. However, some studies show that these medications might be even more likely to result in moderate to severe sexual dysfunction. However, there are medications in trials that appear to show an improved profile in regard to sexual dysfunction and other key side effects.

MAO inhibitors can produce a potentially lethal hypertensive reaction if taken with foods that contain high levels of tyramine, such as mature cheese, cured meats or yeast extracts. In organic Chemistry tyramine (4-hydroxy- Phenethylamine, para-tyramine p-tyramine is a Monoamine compound derived from the Likewise, lethal reactions to both prescription and over the counter medications have occurred. Any patient currently undergoing therapy with an MAO inhibiting medication should be monitored closely by the prescribing physician and always consulted before taking an over the counter or prescribed medication. Such patients should also inform emergency room personnel and information should be kept with one's identification indicating the fact that the holder is on MAO inhibiting medications. Some doctors even suggest the use of a medical alert ID bracelet. Although the reactions in question are dramatic when they happen, the total number of deaths due to interactions and dietary concerns are comparable to over-the-counter medications.

Antidepressants should be used with great care, usually in conjunction with mood stabilisers, in the treatment of bipolar disorder, as they can exacerbate symptoms of mania. This article refers to the medication For other uses see Stabilizer. Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition They have also been known to trigger mania or hypomania in some patients with bipolar disorder and in a small percentage of patients with depression. Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition This article is an expansion of a section entitled '''Hypomania''' from within the main article Bipolar disorder. [15] SSRIs are the antidepressants most frequently associated with this side effect.

In particular, it has been noted that the most dangerous period for suicide in a patient with depression is immediately after treatment has commenced, as antidepressants may reduce the symptoms of depression such as psychomotor retardation or lack of motivation before mood starts to improve. Psychomotor retardation comprises a slowing down of Thought and a reduction of physical movements in a person Although this appears to be a paradox, studies indicate the suicidal ideation is a relatively common component of the initial phases of antidepressant therapy, and it may be even more prevalent in younger patients such as pre-adolescents and teenagers. It is strongly recommended that other family members and loved ones monitor the young patient's behavior, especially in the first eight weeks of therapy, for any signs of suicidal ideation or behaviors.

Until the black box warnings on these drugs were issued by FDA as well as by agencies in other nations, side effects and alerting families to risk were largely ignored and downplayed by manufacturers and practitioners. This may have resulted in some deaths by suicide although direct proof for such a link is largely anecdotal. The higher incidence of suicide ideation reported in a number of studies has drawn attention and caution in how these drugs are used.

People under the age of 24 who suffer from depression are warned that the use of antidepressants could increase the risk of suicidal thoughts and behaviour. Federal health officials unveiled Proposed changes to the labels on antidepressant drugs in December 2006 to warn people of the inherent danger.

On September 6, 2007, the Centers for Disease Control and Prevention reported suicide rate in American adolescents (especially girls, 10 to 24 years old) increased 8% (2003 to 2004), the largest jump in 15 years. The Centers for Disease Control and Prevention (or CDC) is an agency of the United States Department of Health and Human Services based in unincorporated The United States of America —commonly referred to as the The Adolescents are a Hardcore punk band formed in 1980 in Fullerton, California. A girl is any Female Human from birth through Childhood and Adolescence to attainment of Adulthood The term may also be used to mean [90] Specifically, in 2004 - 4,599 suicides in Americans ages 10 to 24, up from 4,232 in 2003, for a rate of 7. 32 per 100,000 people that age. Before, the rate dropped to 6. 78 per 100,000 in 2003 from 9. 48 per 100,000 in 1990. The findings also reinforced the fact that antidepressant drugs reduce suicide risk. Psychiatrists found that the increase is due to the decline in prescriptions of antidepressant drugs like Prozac to young people since 2003, leaving more cases of serious depression untreated. A drug, broadly speaking is any chemical substance that when absorbed into the body Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression In a December 2006 study, The American Journal of Psychiatry said that a decrease in antidepressant prescriptions to minors of just a few percentage points coincided with a 14 percent increase in suicides in the United States; in the Netherlands, the suicide rate was 50% up, upon prescription drop. The American Journal of Psychiatry (AJP is the official journal of the American Psychiatric Association (APA and the most widely read and cited Psychiatric The United States of America —commonly referred to as the The Netherlands ( Dutch:, ˈnedərlɑnt is the European part of the Kingdom of the Netherlands, which consists of the Netherlands the Netherlands [91] The critics of this study contend that the US "2004 suicide figures were compared simplistically with the previous year, rather than examining the change in trends over several years". [92] The pitfalls of such attempts to infer a trend using just two data points (years 2003 and 2004) are further demonstrated by the fact that, according to the new epidemiological data, the suicide rate in 2005 in children and adolescents actually declined despite the continuing decrease of SSRI prescriptions. "It is risky to draw conclusions from limited ecologic analyses of isolated year-to-year fluctuations in antidepressant prescriptions and suicides. One promising epidemiological approach involves examining the associations between trends in psychotropic medication use and suicide over time across a large number of small geographic regions. Until the results of more detailed analyses are known, prudence dictates deferring judgment concerning the public health effects of the FDA warnings. "[93][94] Subsequest follow-up studies have supported the hypothesis that antidepressant drugs reduce suicide risk. [95] [96] However, the conclusion that societal suicide rate decreases are due to antidepressant prescription is extraordinarily dubious given the plethora of confounding variables.

Sexual

Sexual dysfunction is a very common side effect, especially with SSRIs. Sexual dysfunction or sexual malfunction (see also Sexual function) is difficulty during any stage of the Sexual act (which includes desire, Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Common sexual side effects include problems with libido (sexual desire), lack of interest in sex, and anorgasmia (trouble achieving orgasm). Libido in its common usage means Sexual desire however more technical definitions such as those found in the work of Carl Jung, are more general referring to libido Anorgasmia (often related to Delayed ejaculation in males is a form of Sexual dysfunction sometimes classified as a Psychiatric disorder in which the patient [16] Although usually reversible, these sexual side effects can, in rare cases, last for months or years after the drug has been completely withdrawn. This disorder is known as Post SSRI Sexual Dysfunction. Post-SSRI sexual dysfunction (PSSD is an Iatrogenic type of Sexual dysfunction caused directly by the previous use of Selective serotonin reuptake inhibitor

Bupropion, a dual reuptake inhibitor (NE and DA), in many cases results in a moderately increased libido, due to increased dopamine activity. Bupropion ( INN, previously known as amfebutamone; sold as Wellbutrin, Zyban, and several other Trade names is an atypical Antidepressant This effect is also seen with dopamine reuptake inhibitors, CNS stimulants and dopamine agonists, and is due to increases in testosterone production (due to inhibition of prolactin) and increased nitric oxide synthesis. Apomorphine, nefazodone and nitroglycerin have been shown to reverse some sexual dysfunction via increased nitric oxide activity. Nefazodone hydrochloride (trade name Serzone, Nefadar) is an Antidepressant drug marketed by Bristol-Myers Squibb. Nitroglycerin ( NG) ( US spelling also known as nitroglycerine, ( UK Spelling trinitroglycerin, trinitroglycerine MAOIs are reported to have fewer negative effects on sexual function and libido, particularly moclobemide at a 1. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Moclobemide (sold as Aurox, Manerix) is a drug primarily used to treat depression and Social anxiety. 9% rate of occurrence. Betanechol has been reported to reverse MAOI-induced sexual dysfunction via its cholinergic agonist properties (Gross 1982).

In order for the physician to select the appropriate response, the patient should provide the physician with information to distinguish between reduced libido (little or no desire for sex), reduced sexual function (impotence, vaginal dryness) and anorgasmia, as these have separate causes and prompt different treatment. Anorgasmia (often related to Delayed ejaculation in males is a form of Sexual dysfunction sometimes classified as a Psychiatric disorder in which the patient

Thymoanesthesia

Closely related to sexual side effects is the phenomenon of emotional blunting, or mood anesthesia. Many users of SSRIs complain of apathy, lack of motivation, emotional numbness, feelings of detachment, and indifference to surroundings. They may describe this as a feeling of "not caring about anything anymore. " All SSRIs, SNRIs, and serotonergic TCAs are liable to cause this effect to varying degrees, especially at higher dosages.

REM Sleep

It is well recognized that virtually all major antidepressant drugs but trimipramine suppress REM sleep and it has, in fact, been proposed that the clinical efficacy of these drugs largely derives from their suppressant effects on REM sleep. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep. [17] The MAOIs virtually completely abolish REM sleep, while the TCAs and SSRIs have been shown to produce immediate (40-85%) and sustained (30-50%) reductions in REM sleep. Abrupt discontinuation of MAOIs can cause a temporary phenomenon known as "REM rebound" in which the patient experiences extremely vivid dreams and nightmares.

Weight Gain

Many antidepressants in all categories are associated with weight gain usually in the range of 10-50 pounds but not uncommonly upwards of 100 pounds. The specific cause is unknown, but it is known that antidepressants are associated with increased cravings, an inability to feel full despite ingestion of adequate calories, low energy levels and increased daytime sleepiness which can lead to overeating and a lack of desire to exercise, and dry mouth which can lead to ingestion of calorie-laden beverages. Eating low fat, low protein carbohydrate snacks and carbohydrate-rich dinners allows the brain to make serotonin which then controls appetite and balances mood. Carbohydrates thus eaten, as part of a balanced diet, by virtue of their effect on brain serotonin levels, thus support weight loss in the setting of antidepressant weight gain. [97][98]

Controversy

Several studies have stimulated doubt about the effectiveness of antidepressants. A 2002 study cited that the difference between antidepressants and placebo is close to negligible. [99]

The paper in question has been severely criticized by independent researchers, however. One reason for this is that it deals almost exclusively with the SSRI class of medication. In leveling criticism against the efficacy of SSRIs, critics state, it is not the best paper, merely the most widely known one. Also, other classes of antidepressants have demonstrated superior efficacy, and it has been argued that this paper is "throwing the baby out with the bathwater", while its thrust should in fact be leveled at the serotonin hypothesis of depression.

Furthermore, not all patients necessarily respond to a given medication, studies do not always address dosage versus drug-placebo differences for those who do. Data submitted to the FDA can also underestimate how a drug will perform in clinic practice, as studies sometimes are designed as much for marketing purposes as they are to estimate the magnitude of a medication's effects. [100]

Through a Freedom of Information Act request, two psychologists obtained 47 studies used by the FDA for approval of the six antidepressants prescribed most widely between 1987-99. Overall, antidepressant pills worked 18% better than placebos, a statistically significant difference, "but not meaningful for people in clinical settings", says University of Connecticut psychologist Irving Kirsch. He and co-author Thomas Moore released their findings in "Prevention and Treatment", an e-journal of the American Psychological Association. [18]

More than half of the 47 studies found that patients on antidepressants improved no more than those on placebos, Kirsch says. "They should have told the American public about this. The drugs have been touted as much more effective than they are. " He says studies finding no benefit have been mentioned only on labeling for Celexa, the most recently approved drug. Citalopram is an Antidepressant drug used to treat major depression associated with Mood disorders It is also used on occasion in the treatment The others included in his evaluation: Prozac, Paxil, Zoloft, Effexor and Serzone. Paroxetine (trade names Seroxat, Paxil, Parotin, Aropax, Xetanor, ParoMerck, Rexetin) is a Selective serotonin Venlafaxine (Effexor Efexor is an Antidepressant of the Serotonin-norepinephrine reuptake inhibitor (SNRI class first introduced by Wyeth in 1993 Nefazodone hydrochloride (trade name Serzone, Nefadar) is an Antidepressant drug marketed by Bristol-Myers Squibb.

Dr Joseph Glenmullen, a Harvard psychiatrist, has written a book on the subject for the layperson; see link below.

In 2005, anti-depressants became the most prescribed drug in the United States, causing more debate over the issue. Some doctors believe this is a positive sign that people are finally seeking help for their issues. Others disagree, saying that this shows that people are becoming too dependent on anti-depressants. [19]

Lawsuits

In many cases SSRI drug manufacturers have withheld information from the FDA and the public to play down the risks and adverse effects associated with SSRIs. This had led to litigation against many of the pharmaceutical manufacturers of SSRI anti-depressants in cases covering suicidality, SSRI withdrawal and birth defects in neonates from nursing mothers on SSRIs.

In one of the only three cases to ever go to trial for SSRI indication in suicide, Eli Lilly was caught corrupting the judicial process by making a deal with the plaintiff's attorney to throw the case, in part by not disclosing damaging evidence to the jury. The case, known as the Fentress Case involved a Kentucky man, Joseph Wesbecker, on Prozac, who went to his workplace and opened fire with an assault rifle killing 8 people (including Fentress), and injuring 12 others before turning the gun on himself. The Standard Gravure shooting occurred on September 14 1989 when Joseph Wesbecker entered Standard Gravure his workplace and killed eight people injured 12 The jury returned a 9-to-3 verdict in favor of Lilly. The judge, in the end, took the matter to the Kentucky Supreme Court, which found that "there was a serious lack of candor with the trial court and there may have been deception, bad faith conduct, abuse of judicial process and, perhaps even fraud. " The judge later revoked the verdict and instead, recorded the case as settled. The value of the secret settlement deal has never been disclosed, but was reportedly "tremendous". [101]

On December 22, 2006, a US court decided in Hoorman, et al. v. SmithKline Beecham Corp. that individuals who purchased Paxil(R) or Paxil CR(TM) (paroxetine) for a minor child may be eligible for benefits under a $63. 8 million Proposed Settlement. The lawsuit won the claim that pharmaceutical maker GlaxoSmithKline (GSK) promoted Paxil(R) or Paxil CR(TM) for prescription to children and adolescents while withholding and concealing material information about the medication's safety and effectiveness for minors. GlaxoSmithKline plc () is a United Kingdom -based pharmaceutical, biological and Healthcare Company. [102]

The lawsuit stemmed from a consumer advocate protest against Paroxetine manufacturer GSK. Since the FDA approved paroxetine in 1992, approximately 5,000 U. S. citizens – and thousands more worldwide – have sued GSK. Most of these people feel they were not sufficiently warned in advance of the drug's side effects and addictive properties.

According to the Paxil Protest website, hundreds more lawsuits have been filed against GSK. [103] The Paxil Protest website was launched August 8, 2005 to offer both information about the protest and information on Paxil previously unavailable to the public. Events 1220 - Sweden is defeated by Estonian tribes in the Battle of Lihula. Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. Just three weeks after its launch, the site received more than a quarter of a million hits.

The original Paxil Protest website is no longer available. It is understood that the action to remove the site from the internet was undertaken as part of a confidentiality agreement or 'gagging order' which the owner of the site entered into as part of a settlement of his action against GlaxoSmithKline. A gag order (or suppression order) is an order sometimes a legal order by a court or government other times a private order by an employer or other institution restricting (However, in March 2007, the website Seroxat Secrets [20]discovered that an archive of Paxil Protest site [21]was still available on the internet via Archive. org) Gagging orders are common in such cases and can extend to documents that defendants wish to remain hidden from the public. However, in some cases, such documents can become public at a later date, such as those made public by Peter Breggin in February 2006. A press release from Dr. Breggin can be seen here: [22]

In January 2007, according to the Seroxat Secrets website, [23], the national group litigation in the United Kingdom, on behalf of several hundred people who allege withdrawal reactions through their use of the drug Seroxat, against GlaxoSmithKline plc, moved a step closer to the High Court in London, with the confirmation that Public Funding had been reinstated following a decision by the Public Interest Appeal Panel. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located London ( ˈlʌndən is the capital and largest urban area in the United Kingdom. The issue at the heart of this particular action claims Seroxat is a defective drug in that it has a propensity to cause a withdrawal reaction. Hugh James Solicitors confirm this news on their website [24]

On January 29, 2007, the BBC in the UK aired a fourth documentary in its 'Panorama' [25] series about the controversial drug Seroxat. Events 904 - Sergius III comes out of retirement to take over the papacy from the deposed Antipope Christopher. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. This programme, entitled Secrets of the Drug Trials, focuses on three GSK paediatric clinical trials on depressed children and adolescents. The documentary claims Seroxat could not be proven to work for teenagers, and that one clinical trial indicated they were six times more likely to become suicidal after taking it.

Non-mainstream treatments

There are numerous alternative treatments for depression, whether medications or other kinds of intervention.

Opiates

Various Opiates were commonly used as antidepressants until the mid-1950s, when they fell out of favor with medical orthodoxy due to their addictive nature, tolerance buildup issues and their side-effect profile. For other uses see Opiate (disambiguation, or for the class of drugs see Opioid. Today the use of opioids in treating depression is a large taboo in the medical field due to associations with drug abuse; hence, research has proceeded at a very slow rate. A small clinical trial conducted at Harvard Medical School in 1995[26], demonstrated that a majority of treatment-refractory, unipolar, non-psychotic, major depression patients could be successfully treated with an opioid medication called Buprenorphine, which is a partial mu agonist and potent kappa antagonist. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices Harvard Medical School ( HMS) is one of the graduate schools of Harvard University and currently the #1 medical school in America as ranked by U Psychosis (from the Greek ψυχή "psyche" for mind or soul and -οσις "-osis" for abnormal condition with adjective psychotic Buprenorphine (or colloquially "Bupe" is a semi-synthetic Opiate with partial agonist and antagonist actions The exact mechanism of its action in depression is not known, as kappa (κ) antagonists are antidepressants in their own right. Kappa (uppercase &Kappa, lowercase &kappa or ϰ; Κάππα is the 10th letter of the Greek alphabet, used to represent the Voiceless

In 2006, The Journal of European Neuropsychopharmacology published a follow-up study to the 1995 Harvard experiment, with results very consistent with the original Harvard findings. Eleven severely depressed patients, refractory to all the conventional depression treatments, were given small doses of buprenorphine. Most of these patients found the buprenorphine to be of significant benefit in relieving their inner torment. The researchers theorized that "Possibly, the response to opiates describes a special subtype of depressive disorders e. g corresponding to a dysregulation of the endogenous opioid system and not of the monaminergic system. " [27]

Yet another relevant scientific paper was published in the American Journal of Psychiatry in 1999, detailing how researchers found Oxycodone/Oxymorphone to help 5 out of 6 'incurable' refractory severe depression patients. Oxycodone is an Opioid Analgesic Medication synthesized from Thebaine. Oxymorphone ( Opana, Numorphan, Numorphone) or 14-Hydroxydihydro Morphinone is a powerful semi-synthetic Opioid Analgesic [28]

While opioids have been proven to substantially relieve symptoms of depression for a large class of patients, re-acceptance of this fact has been severely hampered by governmental narcotic prohibition efforts, and the (until buprenorphine) lack of alternatives with low risk of tolerance and addiction. The prohibition of drugs through sumptuary Legislation or Religious law is a common means of attempting to control Drug use and the Buprenorphine is generally preferred as the first-line opiate in depression treatment, as managing the tolerance buildup of other opiates can be complicated. Buprenorphine (or colloquially "Bupe" is a semi-synthetic Opiate with partial agonist and antagonist actions

Other treatments

Classes and members

The following clickable info-box is from the Anatomical Therapeutic Chemical Classification System published by the World Health Organization. The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug See also Wikipedia's list of antidepressants. This is a list of Antidepressants by drug group Generic drug names are listed first with trade names in brackets

See also

References

  1. ^ Vega, JA. The number of new Psychiatric drugs, and especially Antidepressants on the market in Japan has significantly lagged behind Western countries , Mortimer, AM. , Tyson, PJ. (2003) Conventional antipsychotic prescription in unipolar depression, I: An audit and recommendations for practice The Journal of clinical psychiatry 64(5), pp. 568-574.
  2. ^ Petty F, Trivedi MH, Fulton M, Rush AJ. (1995) Benzodiazepines as antidepressants: does GABA play a role in depression? Biological Psychiatry. 38(9):578-91
  3. ^ Weber, M. M. & Emrich, H. M. (1988) Current and historical concepts of opiate treatment in psychiatric disorders. International Journal of Clinical Psychopharmacology. Jul;3(3):255-66.
  4. ^ Czygan, F. C. (2003) From a 2500 year old apotropic comes a current antidepressive. The cultural history and mistique of St. John's wort Pharm Unserer Zeit. 32(3):184-90
  5. ^ SELIKOFF IJ, ROBITZEK EH (1952). "Tuberculosis chemotherapy with hydrazine derivatives of isonicotinic acid". Dis Chest 21 (4): 385–438. PMID 14906149.  
  6. ^ a b c Weissman, Myrna M. (2001). Treatment of depression: bridging the 21st century. Washington, D. C: American Psychopathological Association, 10-11. ISBN 0-88048-397-0.  
  7. ^ Healy, David (1996). The Psychopharmacologists: Interviews. London: Chapman & Hall, 8. ISBN 1-86036-008-4.  
  8. ^ Healy, David (1998). The Psychopharmacologists: Volume 2. A Hodder Arnold Publication, 132-134. ISBN 1-86036-010-6.  
  9. ^ ROBITZEK EH, SELIKOFF IJ, MAMLOK E, TENDLAU A (1953). "Isoniazid and its isopropyl derivative in the therapy of tuberculosis in humans: comparative therapeutic and toxicologic properties". Dis Chest 23 (1): 1–15. PMID 12998444.  
  10. ^ a b c d López-Muñoz F, Alamo C, Juckel G, Assion HJ (2007). "Half a century of antidepressant drugs: on the clinical introduction of monoamine oxidase inhibitors, tricyclics, and tetracyclics. Part I: monoamine oxidase inhibitors". J Clin Psychopharmacol 27 (6): 555–9. doi:10.1097/jcp.0b013e3181bb617. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18004120.  
  11. ^ Time Magazine (1957) "Psychic Energizer"
  12. ^ Kuhn, R. (1958) The Treatment of Depressive States with G 22355 (Imipramine Hydrochloride). American Journal of Psychiatry, 115:459-464, November
  13. ^ Biel JH. (1964). Some rationales for the development of antidepressant drugs. Molecular modification in drug design. Adv Chem; 45: 114–39
  14. ^ Pletscher, A. (1991) The discovery of antidepressants: A winding path. Journal of Cellular and Molecular Life Sciences, Volume 47(1)
  15. ^ Healy, D. M. D. (1999)
  16. ^ The Three Faces of the Antidepressants: A Critical Commentary on the Clinical-Economic Context of Diagnosis. Journal of Nervous & Mental Disease. 187(3):174-180
  17. ^ Domino, E. F. (1999) [1] History of Modern Psychopharmacology: A Personal View With an Emphasis on Antidepressants Psychopharmacology and Psychosomatic Research, Special Issue
  18. ^ Wong DT, Bymaster FP, Horng JS, Molloy BB. (1975) [2] A new selective inhibitor for uptake of serotonin into synaptosomes of rat brain: 3-(p-trifluoromethylphenoxy) N-methyl-3-phenylpropylamine]. Journal of Pharmacology and Experimental Therapeutics. 193, p 804–811
  19. ^ Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W & Melchart D (1996) St John’s wort for depression – an overview and meta-analysis of randomised clinical trials. British Medical Journal 313, p253–258.
  20. ^ Muller, W. E. (2003) Current St John's wort research from mode of action to clinical efficacy. Pharmacol Res. Feb;47(2):101-9
  21. ^ Nathan, P. J. (2001) J Hypericum perforatum (St John's Wort): a non-selective reuptake inhibitor? A review of the recent advances in its pharmacology. Psychopharmacol. 2001 Mar;15(1):47-54.
  22. ^ Freeman, H. (1996) Tolerability and safety of novel antidepressants. European Psychiatry, 11(supplement 4), p206.
  23. ^ Lacasse J, Leo J (2005). "Serotonin and depression: a disconnect between the advertisements and the scientific literature". PLoS Med 2 (12): e392. doi:10.1371/journal.pmed.0020392. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16268734.   Full text
  24. ^ Uz T, Ahmed R, Akhisaroglu M, Kurtuncu M, Imbesi M, Dirim Arslan A, Manev H (2005). "Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum". Neuroscience 134 (4): 1309–16. doi:10.1016/j.neuroscience.2005.05.003. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15994025.  
  25. ^ Yuferov V, Butelman E, Kreek M (2005). "Biological clock: biological clocks may modulate drug addiction". Eur J Hum Genet 13 (10): 1101–3. doi:10.1038/sj.ejhg.5201483. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16094306.  
  26. ^ Manev H, Uz T (2006). "Clock genes as a link between addiction and obesity". Eur J Hum Genet 14 (1): 5. doi:10.1038/sj.ejhg.5201524. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16288309.  Full text
  27. ^ www.psychiatrist.com/pcc/pccpdf/v06n04/v06n0403.pdf (PDF).
  28. ^ (National Institute for Clinical Excellence, 2004)
  29. ^ [3]Stagnitti,M. (2005) Antidepressant Use in the US Civilian Non-Insitutionalised Population, 2002. Statistical Brief #77. Rockville,MD: Medical Expenditure Panel, Agency for Healthcare Research and Quality.
  30. ^ Sleath, B. & Shih, YC. (2003) [4] Sociological influences on antidepressant prescribing. Soc Sci Med. Mar;56(6):1335-44.
  31. ^ [5] Depression could be overdiagnosed: Up to 25% may be reacting normally to stresses, study says
  32. ^ Olie JP, Elomari F, Spadone C, Lepine JP. (2002) Antidepressant consumption in the global population in France Encephale. Sep-Oct;28(5 Pt 1):411-7.
  33. ^ Raymond CB, Morgan SG, Caetano PA. (2007) Antidepressant utilization in british columbia from 1996 to 2004: increasing prevalence but not incidence. Psychiatr Serv. 2007 Jan;58(1):79-84.
  34. ^ Meijer W, Heerdink E, Leufkens H, Herings R, Egberts A, Nolen W (2004). "Incidence and determinants of long-term use of antidepressants". Eur J Clin Pharmacol 60 (1): 57–61. doi:10.1007/s00228-004-0726-3. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14985889.  
  35. ^ McManus P, Mant A, Mitchell PB, Montgomery WS, Marley J, Auland ME. (2000) Recent trends in the use of antidepressant drugs in Australia, 1990-1998.Med J Aust. November 6;173(9):458-61.
  36. ^ Mark Zimmerman, Michael Posternak, Michael Friedman, Naureen Attiullah, Scott Baymiller, Robert Boland, Stacie Berlowitz, Shahzad Rahman, Kirsten Uy, Steve Singer (2004) Which Factors Influence Psychiatrists’ Selection of Antidepressants? Am J Psychiatry 161:1285-1289
  37. ^ Petersen T, Dording C, Neault NB, Kornbluh R, Alpert JE, Nierenberg AA, Rosenbaum JF, Fava M. (2002) A survey of prescribing practices in the treatment of depression. Prog Neuropsychopharmacol Biol Psychiatry. Jan;26(1):177-87.
  38. ^ BBC News (July 2002) Male GPs depression pills 'bias'
  39. ^ The number of prescriptions was calculated as the total of prescriptions for the corresponding generic and brand-name drugs using data from the charts for generic and brand-name drugs. Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units.. Drug Topics, Mar 5, 2007. Retrieved on 2007-12-24. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 563 - The Byzantine church Hagia Sophia in Constantinople is dedicated for the second time after being destroyed by Earthquakes
  40. ^ [6] Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000 December 15;20(24):9104-10.
  41. ^ [7]Manev H, Uz T, Smalheiser NR, Manev R. Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro. Eur J Pharmacol. 2001 January 5;411(1-2):67-70.
  42. ^ [8] Uz T, Ahmed R, Akhisaroglu M, Kurtuncu M, Imbesi M, Dirim Arslan A, Manev H. Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum. Neuroscience. 2005;134(4):1309-16.
  43. ^ Zhang HT, Huang Y, Mishler K, Roerig SC, O'Donnell JM. Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor rolipram in rats. Psychopharmacology (Berl). 2005 Oct;182(1):104-15
  44. ^ Carboni L, Vighini M, Piubelli C, Castelletti L, Milli A, Domenici E. Proteomic analysis of rat hippocampus and frontal cortex after chronic treatment with fluoxetine or putative novel antidepressants: CRF1 and NK1 receptor antagonists. Eur Neuropsychopharmacol. 2006 Oct;16(7):521-37.
  45. ^ Carmine M. Pariante, Institute of Psychiatry, King’s College London Depression, stress and the adrenal axis. The British Society for Neuroendocrinology, 2003.
  46. ^ O'Brien SM, Scully P, Scott LV, Dinan TG. "Cytokine profiles in bipolar affective disorder: focus on acutely ill patients. " J Affect Disord. 2006 Feb;90(2-3):263-7.
  47. ^ Obuchowicz E, Marcinowska A, Herman ZS. "Antidepressants and cytokines--clinical and experimental studies" Psychiatr Pol. 2005 Sep-Oct;39(5):921-36.
  48. ^ Hong CJ, Yu YW, Chen TJ, Tsai SJ. "Interleukin-6 genetic polymorphism and Chinese major depression". Neuropsychobiology. 2005;52(4):202-5.
  49. ^ Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP. "Abstract Cytokine dysregulation, inflammation and well-being". Neuroimmunomodulation. 2005;12(5):255-69
  50. ^ Kubera M, Maes M, Kenis G, Kim YK, Lason W. "Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor alpha and interleukin-6" Psychiatry Res. 2005 April 30;134(3):251-8.
  51. ^ Elenkov IJ, Iezzoni DG, Daly A, Harris AG, Chrousos GP. "Cytokine dysregulation, inflammation and well-being". Neuroimmunomodulation. 2005;12(5):255-69
  52. ^ Diamond M, Kelly JP, Connor TJ. "Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade". Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.
  53. ^ Kubera M, Lin AH, Kenis G, Bosmans E, van Bockstaele D, Maes M. "Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. " J Clin Psychopharmacol. 2001 Apr;21(2):199-206
  54. ^ Maes M. "The immunoregulatory effects of antidepressants". Hum Psychopharmacol. 2001 Jan;16(1):95-103
  55. ^ Maes M, Kenis G, Kubera M, De Baets M, Steinbusch H, Bosmans E. "The negative immunoregulatory effects of fluoxetine in relation to the cAMP-dependent PKA pathway". Int Immunopharmacol. 2005 Mar;5(3):609-18.
  56. ^ Brustolim D, Ribeiro-dos-Santos R, Kast RE, Altschuler EL, Soares MB. "A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. " Int Immunopharmacol. 2006 Jun;6(6):903-7
  57. ^ Moulin DE, Clark AJ, Gilron I, Ware MA, Watson CP, Sessle BJ, Coderre T, Morley-Forster PK, Stinson J, Boulanger A, Peng P, Finley GA, Taenzer P, Squire P, Dion D, Cholkan A, Gilani A, Gordon A, Henry J, Jovey R, Lynch M, Mailis-Gagnon A, Panju A, Rollman GB, Velly A; Canadian Pain Society. Pharmacological management of chronic neuropathic pain - consensus statement and guidelines from the Canadian Pain Society. Pain Res Manag. 2007 Spring;12(1):13-21
  58. ^ Jones CK, Eastwood BJ, Need AB, Shannon HE. Analgesic effects of serotonergic, noradrenergic or dual reuptake inhibitors in the carrageenan test in rats: evidence for synergism between serotonergic and noradrenergic reuptake inhibition. Neuropharmacology. 2006 Dec;51(7-8):1172-80.
  59. ^ Kulmatycki KM, Jamali F. "Drug disease interactions: role of inflammatory mediators in depression and variability in antidepressant drug response". J Pharm Pharm Sci. 2006;9(3):292-306.
  60. ^ O'Brien SM, Scott LV, Dinan TG. "Cytokines: abnormalities in major depression and implications for pharmacological treatment". Hum Psychopharmacol. 2004 Aug;19(6):397-403.
  61. ^ Anderson IM (2000) Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability Journal of Affective Disorders. 58(1), 19-3
  62. ^ MacGillivray, S. , Arroll,B. , Hatcher,S. , Ogston,S. , Reid,I. , Sullivan, F. , Williams,B. , Crombie,I. (2003) Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis BMJ. May 10; 326(7397): 1014.
  63. ^ Parker G, Roy K, Wilhelm K, Mitchell P. (2001) Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study. J Clin Psychiatry. Feb;62(2):117-25.
  64. ^ Moncrieff J, Wessely S, Hardy R. (2004) Active placebos versus antidepressants for depression. Cochrane Database Syst Rev. (1):CD003012.
  65. ^ Lotufo-Neto, F. , Trivedi, M. , & Thase, M. E. (1999) Meta-Analysis of the Reversible Inhibitors of Monoamine Oxidase Type A Moclobemide and Brofaromine for the Treatment of Depression Neuropsychopharmacology 20 226-247. 10. 1038
  66. ^ Linde K, Mulrow CD, Berner M, Egger M. (2005) St John's wort for depression. Cochrane Database Syst Rev. 2005 April 18;(2):CD000448.
  67. ^ Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. (2004) Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004 April 10;328(7444):879-83.
  68. ^ Lakhan SE; Hagger-Johnson G. The impact of prescribed psychotropics on youth. Clinical Practice and Epidemiology in Mental Health 2007;3(21).
  69. ^ Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. (2008) Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. Jan 17;358(3):252-60. PMID 18199864
  70. ^ Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT (2008). "Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration". PLoS Med. 5 (2): e45. doi:10.1371/journal.pmed.0050045. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18303940.  
  71. ^ http://www.guidelines.gov/summary/summary.aspx?doc_id=2605&nbr=1831
  72. ^ http://www.nice.org.uk/guidance/CG23
  73. ^ Baghai, TC. , Moller, HJ, Rupprecht, R. (2006) Recent progress in pharmacological and non-pharmacological treatment options of major depression. Curr Pharm Des.  ;12(4):503-15.
  74. ^ a b Ruhe HG, Huyser J, Swinkels JA, Schene AH. (2006)Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. Dec;67(12):1836-55.
  75. ^ Tranter, R. , O'Donovan, CO. , Chandarana, P. , Kennedy, S. (2002) Prevalence and outcome of partial remission in depression J Psychiatry Neurosci. July; 27(4): 241–247.
  76. ^ Byrne, SE. & Rothschild, AJ. (1999) Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments. J Clin Psychiatry. Jun;59(6):279-88.
  77. ^ Mischoulon D, Nierenberg AA, Kizilbash L, Rosenbaum JF, Fava M. (2000) Strategies for managing depression refractory to selective serotonin reuptake inhibitor treatment: a survey of clinicians. Can J Psychiatry. Jun;45(5):476-81.
  78. ^ DeBattista C, Lembke A. (2005) Update on augmentation of antidepressant response in resistant depression. Curr Psychiatry Rep. Dec;7(6):435-40.
  79. ^ Lam RW, Wan DD, Cohen NL, Kennedy SH. (2002) Combining antidepressants for treatment-resistant depression: a review. J Clin Psychiatry. Aug;63(8):685-93.
  80. ^ Geddes JR et al. (2003) Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. February 22;361(9358):653-61.
  81. ^ Fava GA, Park SK, Sonino N. (2006) Treatment of recurrent depression. Expert Rev Neurother. Nov;6(11):1735-40.
  82. ^ Peterson, TJ. (2006) Enhancing the efficacy of antidepressants with psychotherapy Journal of Psychopharmacology, Vol. 20, No. 3 suppl, 19-28, 2006
  83. ^ Trivedi MH, Rush AJ, Wisniewski SR, et al (2006). "Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice". The American journal of psychiatry 163 (1): 28–40. doi:10.1176/appi.ajp.163.1.28. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16390886.  
  84. ^ Trivedi MH, Fava M, Wisniewski SR, et al (2006). "Medication augmentation after the failure of SSRIs for depression". N. Engl. J. Med. 354 (12): 1243–52. doi:10.1056/NEJMoa052964. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16554526.  
  85. ^ Rush AJ, Trivedi MH, Wisniewski SR, et al (2006). "Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression". N. Engl. J. Med. 354 (12): 1231–42. doi:10.1056/NEJMoa052963. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16554525.  
  86. ^ Cohen, MD, Lee S. ; Lori L. Altshuler, MD; Bernard L. Harlow, PhD; Ruta Nonacs, MD, PhD; D. Jeffrey Newport, MD; Adele C. Viguera, MD; Rita Suri, MD; Vivien K. Burt, MD, PhD; Victoria Hendrick, MD; Alison M. Reminick, BA; Ada Loughead, BA; Allison F. Vitonis, BA; Zachary N. Stowe, MD (February 1, 2006). "Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment". Journal of the American Medical Association 295 (5): 499–507. American Medical Association. doi:10.1001/jama.295.5.499. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16449615.  
  87. ^ "Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment—Correction" (July 12, 2006). JAMA 296 (2): 170. doi:10.1001/jama.296.2.170. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  88. ^ David Armstrong, "Drug Interactions: Financial Ties to Industry Cloud Major Depression Study At Issue: Whether It's Safe For Pregnant Women To Stay on Medication - JAMA Asks Authors to Explain". Wall Street Journal. July 11, 2006 (copy published on post-gazette. com)
  89. ^ Lenzer, Jeanne (2006). "Antidepressants double suicidality in children, says FDA". BMJ 332: 626. doi:10.1136/bmj.332.7542.626-c. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  90. ^ Suicide Rises in Youth; Antidepressant Debate Looms, Benedict Carey, New York Times, September 7, 2007
  91. ^ Simon GE, Savarino J, Operskalski B, Wang PS (2006). "Suicide risk during antidepressant treatment". Am J Psychiatry 163 (1): 41–7. doi:10.1176/appi.ajp.163.1.41. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16390887.  
  92. ^ Jureidini J (2007). "The black box warning: decreased prescriptions and increased youth suicide?". Am J Psychiatry 164 (12): 1907. doi:10.1176/appi.ajp.2007.07091463. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18056248.  
  93. ^ Olfson M, Shaffer D (2007). "SSRI Prescriptions and the Rate of Suicide". Am J Psychiatry 164 (12): 1907–1908. doi:10.1176/appi.ajp.2007.07091467. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18056247.  
  94. ^ Kung HC, Hoyert DL, Xu J, Murphy SL. N C H S - Health E Stats - Deaths: Preliminary Data for 2005 (htm). National Center for Health Statistics. Retrieved on 2007-12-12. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 627 - Battle of Nineveh: A Byzantine army under Emperor Heraclius defeats Emperor Khosrau II 's Persian
  95. ^ Bridge JA, Iyengar S, Salary CB, et al (2007). "Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials". JAMA 297 (15): 1683–96. doi:10.1001/jama.297.15.1683. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17440145.  
  96. ^ Beasley CM, Ball SG, Nilsson ME, et al (2007). "Fluoxetine and Adult Suicidality Revisited: An Updated Meta-Analysis Using Expanded Data Sources From Placebo-Controlled Trials". J Clin Psychopharmacol 27 (6): 682–686. doi:10.1097/jcp.0b013e31815abf21. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18004137.  
  97. ^ Wurtman, J. , Wurtman R. , McDermott J. , Levendusky P and Duca K. (2002). The Effect of a Novel Dietary Intervention on Weight Loss in Psychotropic Drug-Induced Obesity. Psychopharmacology Bulletin Vol. 36 No. 3 p. 55-59
  98. ^ Wurtman, J. Marquis, N (2007) The Serotonin Power Diet, Rodale Books.
  99. ^ [9]Kirsch I, Moore TJ, Scoboria A, Nicholls SS (2002a), The emperor's new drugs: an analysis of antidepressant medication data submitted to the U. S. Food and Drug Administration. Prevention & Treatment 5:Article 23
  100. ^ Hollon, Steven D. ; DeRubeis, Robert J. ; Shelton, Richard C. ; Weiss, Bahr The emperor's new drugs: Effect size and moderation effects. Prevention & Treatment. 5(1), July 2002, No Pagination Specified.
  101. ^ [10] from Richard Zitrin & Carol M. Langford. "Hide and Secrets in Louisville" from "The Moral Compass of the American Lawyer". Ballantine Books, 1999
  102. ^ [11] October 1998 GSK Internal Memo: Strategy of Concealment
  103. ^ [12] Newstarget September 6, 2005
  104. ^ World Health Organisation, Acupuncture: Review and Analysis of Reports on Controlled Clinical Trials, 2002
  105. ^ ABC Australia Science News on acupuncuture.
  106. ^ Hypericum Depression Trial Study Group (2002). Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder: A Randomized Controlled Clinical Trial. JAMA, 287 (14):1807-1814
  107. ^ Roberto Delle Chiaie, Paolo Pancheri and Pierluigi Scapicchio. (2002). Efficacy and tolerability of oral and intramuscular S-adenosyl- L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr, 76 (5): 1172S-1176S
  108. ^ Mischoulon D, Fava M. (2002). Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr, 76 (5): 1158S-61S.
  109. ^ "Drug 'treats depression in hours'", BBC, 2006-08-07. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 322 BC - Battle of Crannon between Athens and Macedon following the death of Alexander the Great. Retrieved on 2006-09-17. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1176 - The Battle of Myriokephalon is fought 1462 - The Battle of Świecino (or Battle of Żarnowiec  

Additional reading

External links

Events 197 - Roman Emperor Septimius Severus defeats usurper Clodius Albinus in the Battle of Lugdunum

Dictionary

antidepressant

-noun

  1. An agent that prevents or counteracts depression.

-adjective

  1. Preventing or counteracting depression.
© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
 Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic