Antidepressants are drugs used for the treatment of major depressive disorders and other conditions, including dysthymia, anxiety disorders, obsessive-compulsive disorders, eating disorders, chronic pain, neuropathic pain and, in some cases, dysmenorrhoea, snoring, migraines, attention-conscious hyperactivity disorder (ADHD), addiction, dependence, and sleep disturbance. They may be prescribed alone or in combination with other drugs.
Some of the typical side effects of antidepressants are dry mouth, weight gain, and lack of sexual drive. Some antidepressants may even cause infertility in both men and women depending on how long the drug is taken or how the body reacts to the drug. Most types of antidepressants are usually safe to eat, but can cause increased thoughts of suicide. When prescribing antidepressants, your doctor will warn people not to stop taking medication or miss a few doses at a time; this can cause symptoms similar to major withdrawal, and stop taking medication suddenly may aggravate depression. Patients are even encouraged to communicate and work with their doctors to break away from the drug by gradually and safely reducing the dose when needed.
The most important classes of antidepressants are selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCA), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), tetracyclic antidepressants TeCA), and noradrenergic and specific serotonergic antidepressants (NaSSAs). St. John's wort is also used in the treatment of depression.
One theory about the cause of depression is that it is characterized by an exaggerated hypothalamus-pituitary-adrenal axis (HPA axis) that resembles a neuro-endocrine response to stress. This HPA axis disorder participates in the development of depressive symptoms, and antidepressants may serve to regulate the HPA axis function.
There is a lengthy debate in the medical community about the effectiveness of antidepressants, centered around whether the results observed in patients can be attributed to a placebo effect.
Video Antidepressant
Medical use
For depression, the Hamilton Depression Rating Scale (HAM-D) is often used to measure the severity of depression. The maximum score for the 17-item Human-D questionnaire is 52; the higher the score, the more severe the depression.
Major depressive disorder
Clinical guidelines
The 2009 UK National Institute for Health and Care Excellence (NICE) guidelines show that antidepressants should not be used routinely for early treatment of mild depression, because of the risk-benefit ratio. Guidelines recommend that antidepressant treatment be considered for:
- People with moderate or severe depression,
- Those with mild depression have been present for a long time,
- As second-line treatment for mild depression that continues after another intervention,
- As a first-line treatment for moderate or severe depression.
The guidelines further note that antidepressant treatment should be used in combination with psychosocial intervention in many cases, should be continued for at least six months to reduce the risk of recurrence, and that SSRIs are usually more tolerable than other antidepressants.
The American Psychiatric Association's treatment guidelines recommend that initial care should be individually adjusted based on factors including symptoms severity, existing disorders, previous care experience, and patient preferences. Options may include pharmacotherapy, psychotherapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or light therapy. They recommend antidepressant drugs as an initial treatment option in people with mild, moderate, or severe depression, which should be given to all patients with severe depression unless ECT is planned.
Systematic review
Conflicting results have emerged from studies that analyze the effectiveness of antidepressants by comparison to placebo in people with mild to moderate acute depression. Strong evidence supports the usefulness of antidepressants in the treatment of chronic (dysthymia) or severe depression.
A meta-analysis analysis in 2018 found that in adults with depressive depressive depressive antidepressants more efficacious than placebo. Measures of effect measured at 8-weeks after treatment onset were modest with an average difference of 0.3 standard difference.
A 2017 meta-analysis comparing the efficacy of SSRIs against placebo found an average decrease in the Hamilton Depression Rating Scale (HDRS) to -1.94 points above 49 studies. This is statistically significant, but fails to meet the clinical significance threshold, which is set in accordance with the National Institute for Health and Nursing Excellence recommends a standard difference in standard 0.5, equivalent to 3-point reduction in HDRS. A high bias risk was found, which might explain the statistically significant SSRI effect, and the authors concluded that the frequency of adverse events exceeded minor clinical improvement.
A systematic review of adjunctive therapy conducted in 2015 for treatment-resistant depression concluded that quetiapine and aripiprazole had the strongest evidence base that supported their efficacy, but they were associated with additional treatment-related side-effects when used as adjunctive therapy.
In 2014 the US FDA published a systematic review of all trials of antidepressant treatments submitted to agencies between 1985 and 2012. The authors concluded that treatment care reduced the risk of relapse by 52% compared with placebo, and that this effect was mainly due to recurrent depression in the placebo group rather than the drug withdrawal effect.
A 2012 meta-analysis found that fluoxetine and venlafaxine are effective for severe depression in all age groups. The authors also found no evidence of a relationship between the severity of depression and the level of antidepressant benefits against placebo.
A review published in 2012 found a negative correlation between the study year and antidepressant efficacy as measured by response rates. Changes in response rates were largely driven by increased placebo response. However the authors still conclude that antidepressants are effective in treating depression. The authors found that TCA is the most effective drug, followed by SNRI, MAOIs, SSRIs and atypical antidepressants.
The Cochrane Collaboration publishes a systematic review of clinical trials of tricyclic antidepressant amitriptyline in 2012. The study concludes that regardless of moderate evidence for publication bias, there is strong evidence that the efficacy of amitriptyline is superior to placebo.
The efficacy of paroxetine (Paxil) and imipramine observed in the 2010 meta-analysis became dependent on the initial severity, as measured by HDRS. Antidepressants in patients with scores less than 23 (indicating mild to moderate depression) showed little benefit compared with placebo. However, antidepressants in those with scores & gt; 25 showed an advantage over placebo crossing the NICE threshold for clinical significance.
A review commissioned by the National Institute for Health and Care Excellence published in 2009 concluded that there is strong evidence that SSRIs have greater efficacy than placebo in achieving a 50% reduction in depression scores in moderate and severe depression, and that there are some evidence for a similar effect in mild depression. Treatment guidelines developed along with these reviews indicate that antidepressants should be considered in patients with moderate to severe depression and those with mild depression who are persistent or resistant to other treatment modalities.
A review of Collaboration Cochrane 2008 on St. John's Wort (in particular, any extract containing Hypericum perforatum ), and a 2015 meta-analytic systematic review by some of the same authors, both concluded that: having superior efficacy for placebo in treat depression; as effective as standard antidepressant drugs to treat depression; and has fewer side effects than other antidepressants. The 2015 meta analysis concludes that it is difficult to establish a place for St. John's wort in the treatment of depression due to limitations in the available evidence base, including the large variations in success seen in trials conducted in German speaking relative to other countries. Reversible inhibitors of monoamine oxidase A (RIMAs) have also been shown to be effective drug therapy with greater tolerability than other antidepressants; However, the efficacy of SSRIs, tricyclics, and tetracyclic antidepressants in treating depression is supported by a much larger evidence base than other antidepressant drug therapies (ie, St John Wort, rMAO-A inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonin antagonists and reuptake inhibitors , noradrenaline reuptake inhibitors, and certain noradrenergic and serotonergic antidepressants).
In the publication of 2008, Irving Kirsch and Thomas Moore concluded that the overall effect of a new generation antidepressant drug falls under the recommended criteria for clinical significance. The updated work was first published in 2002 in which they stated that the most consistent evidence plays a role as an active placebo.
The 2004 review concluded that antidepressant studies that failed to support claims of efficacy were dramatically less likely to be published than those favoring favorable efficacy claims. Similar results were obtained for the study of antidepressant clinical trial publication in children. The investigation of meta-analysis of antidepressant studies in 2015 found that 79% of them had "sponsors or authors who were industrial employees (or pharmaceuticals) and/or had a conflict of interest".
A study published in the Journal of the American Medical Association JAMA in 2002 showed that the magnitude of placebo effect in clinical trials of depression has evolved over time, while the effect size of the drug tested remains relatively constant. The authors suggest that one possible explanation for the placebo effect that develops in clinical trials is the inclusion of larger numbers of participants with short, mild, or spontaneous depression caused by decreased stigma associated with antidepressant use. The rate of placebo response in clinical trials of complementary and alternative therapies (CAM) was significantly lower than in traditional antidepressant clinical trials.
Test STAR * D
The largest and most expensive study conducted to date, on the effectiveness of pharmacological treatment for depression, was commissioned by the National Institute of Mental Health. The study was dubbed "The Sequenced Treatment Alternatives to Relief Depression" (STAR). The results are summarized here. Participants in the trial are recruited when they seek medical care at a general medical or psychiatric clinic. No ads are used to recruit a subject to maximize the generalization of the study results. Participants are required to have a minimum score of 14 points on the Hamilton Depression Scale (HAM-D17) in order to be enrolled in the trial. Commonly received snippets are 7-17 points for mild depression, 18-24 points for moderate depression, and> = 24 for major depression. The average score of the participants of HAM-D17 is 22. The primary predefined endpoint of this trial is remission as determined by the HAM-D score, with all patients with missing values ​​assessed as non-responders. In the aftermath of the trial, researchers have presented results primarily using secondary endpoint remissions according to QIDS-SR16 Score, which tend to be somewhat higher.
- After the first treatment, 27.5% of 2,876 participants achieved remission with a HAM-D score of 7 or less and 33% achieved remission according to QIDS-SR scale. The response rate according to the QIDS-SR16 score was 47%. Twenty six percent out.
- After the second treatment, 21 to 30% of the remaining 1,439 participants were sent. The transition of drugs can achieve remission in about 25% of patients.
- After the third training, 17.8% of the remaining 310 participants were sent.
- After the fourth and final treatment, 10.1% of the remaining 109 participants were sent.
- Relapse within 12 months was 33% in those who achieved remission in the first stage, and 42% to 50% in those who achieved remission in later stages. Relapse was higher in those who responded to the drug but did not achieve remission (59-83%) than in those who achieved remission.
There were no clinical or significant differences in remission rates, response rates, or time to remission or response among any drugs compared in this study. These include ongoing bupropion releases, bupropion, citalopram, lithium, mirtazapine, nortriptyline, sertraline, triiodothyronine, tranylcypromine, and extended release of venlafaxine.
A 2008 review of randomized controlled trials concluded that symptomatic improvement with the largest SSRI occurred at the end of the first week of use, but some improvement continued for at least 6 weeks.
Limits and strategies
Between 30% and 50% of individuals treated with antidepressants given did not show a response. In clinical studies, about one-third of patients achieve full remission, one-third responded and a third did not respond. Partial remission is characterized by the presence of residual symptoms that are not clear. These symptoms usually include feelings of depression, psychic anxiety, sleep disorders, fatigue and decreased interest or pleasure. At present it is not clear which factors predict partial remissions. However, it is clear that residual symptoms are a strong predictor of relapse, with recurrence rates 3-6 times higher in patients with residual symptoms than in those with full remission. In addition, antidepressant drugs tend to lose effectiveness during treatment. According to data from the Centers for Disease Control and Prevention, fewer than a third of Americans who took an antidepressant drug had seen a mental health professional in the previous year. A number of strategies are used in clinical practice to try to overcome these limitations and variations. They include drug switches, augmentation, and combinations.
"Trial and error" switch
The American Psychiatric Association 2000 Guidelines Guidelines suggest that where no response is achieved after six to eight weeks of treatment with antidepressants, to switch to antidepressants in the same class, then to different antidepressant classes. The 2006 meta-analysis study found wide variations in previous research findings; for patients failing to respond to SSRI antidepressants, between 12% and 86% showed a response to new drugs. However, the more antidepressants someone has tried, the less likely they are to benefit from a new antidepressant trial. However, later meta-analyzes found no difference between switching to new drugs and still using old drugs; Although 34% of treatment-resistant patients responded when switching to new drugs, 40% responded without being exchanged.
Augmentation and combination
For some of the responses, the American Psychiatric Association guidelines suggest augmentation, or add drugs from different classes. These include lithium and thyroid augmentation, dopamine agonists, sex steroids, NRIs, glucocorticoid-specific agents, or newer anticonvulsants.
Combination strategies involve the addition of other antidepressants, usually from different classes so as to have an effect on other mechanisms. Although this can be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy. Other recent tests include the use of psychostimulants as an augmentation therapy. Several studies have demonstrated the efficacy of combining modafinil with treatment-resistant patients. This has been used to help combat fatigue related SSRIs.
Long-term use
The antidepressant therapeutic effect usually does not continue after treatment is over. This results in a high recurrence rate. A 2003 meta-analysis of 31 placebo-controlled antidepressant trials, largely confined to studies covering a one-year period, found that 18% of patients who responded to antidepressants relapsed while still using them, compared with 41% whose antidepressants were diverted to placebo.
The gradual loss of therapeutic benefits occurs in a small number of people during treatment. Strategies involving the use of pharmacotherapy in the treatment of acute episodes, followed by psychotherapy in the residual phase, have been suggested by several studies.
Anxiety disorder
General anxiety disorder
Antidepressants are recommended by the National Institute for Health and Nursing Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder whose main feature is excessive concern about a number of different events. The main symptoms include excessive anxiety about some events and problems, and difficulty controlling an alarming mind that lasts for at least 6 months.
Antidepressants provide moderate-to-moderate reduction in anxiety in GAD, and are superior to placebo in treating GAD. The efficacy of different antidepressants is similar.
Obsessive-compulsive disorder
SSRIs are second-line treatment of obsessive-compulsive disorder (OCD) with mild functional impairment and as first-line treatment for those with moderate or severe disturbances. In children, SSRIs may be considered second-line therapy in those with moderate to severe disturbances, with close monitoring for psychiatric side-effects. SSRI efficacious in the treatment of OCD; patients treated with SSRIs were about twice as likely to respond to treatment as treated with placebo. Efficacy has been shown to be good in short-term treatment trials for 6 to 24 weeks and in stopping trials for 28 to 52 weeks.
Feeding disorders
Antidepressants are recommended as alternatives or additional first steps for self-help programs in the treatment of bulimia nervosa. SSRIs (especially fluoxetine) are preferred over other antidepressants because of the ability to receive, tolerability, and reduction of superior symptoms in short-term trials. Long-term efficacy is still poorly characterized. Bupropion is not recommended for the treatment of eating disorders due to an increased risk of seizures.
Similar recommendations apply to eating disorders. SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.
Clinical trials have produced most of the negative results for SSRI use in the treatment of anorexia nervosa. Nursing guidelines from the National Institute of Health and Care Excellence recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association note that SSRIs do not give any benefit to weight gain, but they can be used to treat any depressive, anxiety, or obsessive-compulsive disorder.
Pain
Fibromyalgia
A 2012 meta-analysis concluded that antidepressant treatment benefits benefitting pain, health-related quality of life, depression, and sleep in fibromyalgia syndrome. Tricyclics appears to be the most effective class, with a moderate effect on pain and sleep and a small effect on fatigue and quality of life related to health. The fraction of people who experienced a 30% reduction in pain in tricyclics was 48% versus 28% for placebo. For SSRI and SNRI, the fraction of people who experienced 30% reduction in pain was 36% (20% in the placebo comparator arm) and 42% (32% in the appropriate placebo comparator arm). Discontinuation of treatment due to side effects is common. Antidepressants including amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole are recommended by the European League Against Rheumatism (EULAR) for the treatment of fibromyalgia based on "limited evidence".
Neuropathic pain
2014 Meta-analysis of Cochrane Collaboration found duloxetine antidepressants to be effective for the treatment of pain due to diabetic neuropathy. The same group reviewed the data for amitriptyline in the treatment of neuropathic pain and found a limited, useful, randomized, clinical trial data. They concluded that the long history of successful use in society for the treatment of fibromyalgia and neuropathic pain justified its continued use. The group is worried about the possibility of exaggerating the amount of pain relief provided by amitriptyline, and highlights that only a small number of people will experience significant pain relief by taking this drug.
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Antidepressants may be helpful for treating people with depression and alcohol dependence, but evidence supporting this association is of poor quality.
Maps Antidepressant
Adverse health effects
Difficulty tolerating side effects is the most common reason for the termination of antidepressants.
General
Virtually all drugs involved with serotonin regulation have the potential to cause serotonin toxicity (also known as serotonin syndrome) - excess serotonin that can cause mania, anxiety, agitation, labile emotions, insomnia and confusion of its main symptoms. Although this condition is serious, it is not very common, it generally only appears at high doses or when using other drugs. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal.
MAOI tend to have a clear (sometimes fatal) interaction with a variety of over-the-counter medications and drugs. If taken with foods containing very high levels of tyramine (for example, mature cheese, preserved meat, or yeast extract), they can cause potentially lethal hypertensive crises. At lower doses people may be distracted by just a headache due to an increase in blood pressure.
In response to these adverse effects, different types of MAOI have been developed: reversible inhibitors of the monoamine oxidase A (RIMA) drug class. Their main advantage is that they do not require people to follow a special diet, while supposedly effective as SSRIs and tricyclics in treating depressive disorders.
Pregnancy
The use of SSRIs in pregnancy has been associated with various risks with varying degrees of evidence of cause. Because depression is independently associated with negative pregnancy outcomes, determining the extent to which the observed relationship between antidepressant use and certain adverse outcomes reflects the causative relationship has been difficult in some cases. In other cases, the attribution of adverse outcomes to antidepressant exposure seems fairly obvious.
The use of SSRIs in pregnancy was associated with an increased risk of spontaneous abortion around 1.7-fold, and was associated with preterm delivery and low birth weight.
A systematic review of the risk of major birth defects in antidepressant-exposed pregnancies found a small increase (3% to 24%) in the risk of major malformations and the risk of cardiovascular birth defects that did not differ from unexposed pregnancies. A study of pregnancies exposed to fluoxetine found a 12% increase in the risk of major malformations that have just lost statistical significance. Other studies have found an increased risk of cardiovascular birth defects among depressed mothers who did not undergo SSRI treatment, suggesting a possible bias of determination, for example. that worried mothers may pursue more aggressive testing of their babies. Other studies found no improvement in cardiovascular birth defects and a 27% increased risk of major malformations in SSRI exposed pregnancies. The FDA recommends for the risk of birth defects with the use of paroxetine and MAOI should be avoided.
A systematic review and meta-analysis 2013 found that antidepressant use during pregnancy was statistically significantly associated with some pregnancy outcomes, such as gestational age and preterm birth, but not with other outcomes. The same review warns that due to differences between exposed and unexposed groups, it is doubtful whether they are clinically significant.
A neonate (baby less than 28 days) may experience withdrawal syndrome from sudden termination of antidepressants at birth. Antidepressants have been shown to be present in varying amounts in breast milk, but the effect on infants is currently unknown.
In addition, SSRIs inhibit the synthesis of nitric oxide, which plays an important role in the regulation of vascular tone. Several studies have shown an increased risk of prematurity associated with SSRI use, and this association may be due to an increased risk of pre-eclampsia pregnancy.
Mania induced by antidepressants
Another possible problem with antidepressants is the possibility of antidepressant induced mania in patients with bipolar disorder. Many cases of bipolar depression are very similar to unipolar depression. Therefore, patients may be misdiagnosed with unipolar depression and given antidepressants. Studies have shown that antidepressant induced mania can occur in 20-40% of bipolar patients. For bipolar depression, antidepressants (most commonly SSRIs) may aggravate or trigger symptoms of hypomania and mania.
Suicide
Studies have shown that antidepressant use correlates with an increased risk of suicidal and thinking (suicidal) behavior in those under 25 years of age. The issue has been serious enough to warrant government intervention by the US Food and Drug Administration (FDA) to warn of an increased risk of suicide during antidepressant treatment. According to the FDA, an increased risk of suicide is within the first month or two of treatment. The National Institute for Health and Nursing Excellence (NICE) places an excess risk in the "early stages of treatment". A meta-analysis shows that the relationship between antidepressant use and suicidal or mind-depending behavior depends on age. Compared with placebo the use of antidepressants was associated with an increase in suicidal or mind-binding behavior among those aged under 25 (OR = 1.62). An increase in the suicidal approach observed in children and adolescents. No effect or mild protective effect among those aged 25 to 64 (OR = 0.79). Antidepressant treatment has a protective effect against suicide among those aged 65 years and over (OR = 0.37).
Sexual
Sexual side effects are also common in SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction. Although usually reversible, these sexual side effects can, in rare cases, last for months or years after the drug has been completely withdrawn.
In the study of 1022 outpatients, the overall sexual dysfunction with all antidepressants averaged 59.1% with an SSRI score between 57 and 73%, 24% mirtazapine, 8% nefazodone, 7% amineptine and 4% moclobemide. Moclobemide, a selective reversible MAO-A inhibitor, does not cause sexual dysfunction, and may in fact lead to an increase in all aspects of sexual function.
The suggested biochemical mechanisms as the cause include increased serotonin, especially those affecting 5-HT recipes 2 and 5-HT 3 ; dopamine degradation; decreased norepinephrine; cholinergic and receptor blockade? 1 adrenergik; inhibition of nitric oxide synthase; and elevated prolactin levels. Mirtazapine is reported to have fewer sexual side effects, most likely due to the 5-HT receptor antagonist 2 and 5-HT 3 and possibly, in some cases, reversed sexual dysfunction induced by SSRI with the same mechanism.
Bupropion, weak NDRI and nicotinic antagonists, may be useful in treating the reduced libido as a result of SSRI treatment.
Changes in weight
Changes in appetite or body weight are common among antidepressants, but are largely dependent on the drug and are associated with the neurotransmitters they influence. Mirtazapine and paroxetine, for example, have an effect of weight gain and/or increased appetite, while others (such as bupropion and venlafaxine) achieve the opposite effect.
The antihistamine properties of certain TCA- and grade-TCA antidepressants have been shown to contribute to the common side effects of appetite increase and weight gain associated with this class of drugs.
Termination syndrome
Symptoms of antidepressant cessation were first reported with imipramine, the first tricyclic antidepressant (TCA), in the late 1950s, and each new class of antidepressants had reported similar conditions, including monoamine oxidase inhibitors (MAOIs), SSRIs, and SNRIs. In 2001, at least 21 different antidepressants, including all major classes, were known to cause termination syndrome. The problem has been poorly learned, and most of the literature is case reports or small clinical studies; incidences are difficult to determine and controversial.
People with termination syndrome have been on antidepressants for at least four weeks and recently stopped taking the drug, either suddenly or after a quick taper. Common symptoms include flu-like symptoms (nausea, vomiting, diarrhea, headache, sweating), sleep disorders (insomnia, nightmares, persistent drowsiness), sensory/movement disturbances (imbalance, tremor, vertigo, dizziness, ), mood disorders (dysphoria, anxiety, agitation) and cognitive impairment (confusion and hyperarousal). More than fifty symptoms have been reported.
Most cases of the last termination syndrome between one and four weeks are relatively mild, and heal by itself; in rare cases, the symptoms can be severe or widespread. Paroxetine and venlafaxine appear to be very difficult to discontinue and a prolonged withdrawal syndrome that lasts for 18 months has been reported with paroxetine.
With the explosion of use and interest in SSRIs in the late 1980s and early 1990s, which focused mainly on Prozac, interest grew also in the termination syndrome. In the late 1990s, some researchers thought that the symptoms that arise when antidepressants are stopped, may mean that antidepressants cause addiction, and some use the term "withdrawal syndrome" to describe symptoms. Addictive substances cause physiological dependence, so cessation of drugs causes suffering. These theories are abandoned, because addiction leads to drug-seeking behavior, and people taking antidepressants do not exhibit drug-seeking behavior. The term "withdrawal syndrome" is no longer used in connection with antidepressants, to avoid confusion with problems arising from addiction. There are reports of antidepressant cases being abused, but these are rare and largely confined to antidepressants with stimulant effects and for people who already have substance use disorders. Comparison of the effect of discontinuation of therapy with benzodiazepines and SSRIs in 2012 suggests that because of similar symptoms, it does not make sense to say that benzodiazepines are addictive while SSRIs do not. The response to the review noted that there is no evidence that people who stop taking SSRIs exhibit drug seeking behavior while people who stop using benzodiazepines, and that drug classes should be considered differently.
Emotional emphasis
Antidepressants can cause embarrassment, emotional, or numbness. This is an extreme emotional reduction, both positive and negative. While patients may feel less depressed, they may also feel unhappy or empathetic in some situations. This may lead to dose reduction or drug changes. The exact mechanism is unknown.
Pharmacology
The earliest and perhaps most widely accepted scientific theory of antidepressant action is the monoamine hypothesis (which can be traced back to the 1950s), which states that depression is caused by an imbalance (most often deficient) of monoamine neurotransmitters (ie serotonin, norepinephrine and dopamine ). It was initially proposed based on the observation that certain hydrazine anti-tuberculosis agents produced antidepressant effects, which were then associated with their inhibitory effects on monoamine oxidase, an enzyme that catalyzes the breakdown of monoamine neurotransmitters. All currently marketed antidepressants have a monoamine hypothesis as their theoretical basis, with the possible exception of agomelatine acting on multiple pathways of serotonergic melatonergics. Regardless of the success of the monoamine hypothesis, it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action at least a week; and second, there is a sizable portion (& gt; 40%) of depressed patients who do not adequately respond to monoaminergic antidepressants. A number of alternative hypotheses have been proposed, including glutamate, neurogenics, epigenetics, cortisol hypersecretion and inflammatory hypotheses.
Type
Selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitors (SSRIs) are believed to increase the extracellular levels of serotonin neurotransmitters by limiting reabsorption into presinaptic cells, increasing serotonin levels in the synaptic clearances available to bind postinaptic receptors. They have varying degrees of selectivity for other monoamine transporters, with pure SSRIs having only a weak affinity for norepinephrine and dopamine transporters.
SSRIs are the most widely prescribed antidepressants in many countries. SSRI efficacy in cases of mild or moderate depression has been disputed.
Serotonin-norepinephrine reuptake inhibitor
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are potential inhibitors of serotonin reuptake and norepinephrine. These neurotransmitters are known to play an important role in mood. SNRI can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act mainly on serotonin alone.
The human serotonin transporter (SERT) and norepinephrine (NET) transporter is a membrane protein responsible for reuptake of serotonin and norepinephrine. A balanced double barrier of monoamine reuptake may offer an advantage over other antidepressant drugs by treating various symptoms.
SNRI is sometimes also used to treat anxiety disorders, obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), chronic neuropathic pain, and fibromyalgia syndrome (FMS), and to relieve menopausal symptoms.
Serotonin modulators and stimulators
Serotonin (SMS) modulators and stimulators (SMS), sometimes referred to as modest serotonin modulators, are a type of drug with specific multimodal measures for the serotonin neurotransmitter system. Precisely, SMS simultaneously modulates one or more serotonin receptors and inhibits serotonin reuptake. This term was coined to describe the mechanism of action of serotonergic antidepressant vortioxetine, which acts as a serotonin reuptake inhibitor (SRI), partial agonist 5-HT receptor 1A , and antagonists of 5 HT 3 and 5-HT 7 receptor. However, it can also be technically applied to vilazodone, which is also an antidepressant and acts as a partial agonist of SRI and 5-HT 1A .
The alternative term is serotonin partial agonist/reuptake inhibitor (SPARI), which can be applied only to vilazodone.
Serotonin antagonists and reuptake inhibitors
Serotonin antagonists and reuptake inhibitors (SARI) while primarily used as antidepressants, are also anxiolytic and hypnotic. They act with antagonist serotonin receptors such as 5-HT 2A and inhibit reuptake of serotonin, norepinephrine, and/or dopamine. In addition, most also act as? 1 -adrenergic receptor antagonist. The majority of SARI marketed today are included in the class of phenylpiperazine compounds. They include trazodone and nefazodone.
Norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitors (NRIs or NERIs) are a type of drug that acts as a reuptake inhibitor for norepinephrine neurotransmitter (noradrenaline) by blocking the action of the norepinephrine (NET) transporter. This in turn leads to an increase in norepinephrine extracellular concentration.
NRI is commonly used in the treatment of conditions such as ADHD and narcolepsy due to the effects of psyostimulan and obesity due to their appetite suppressant effect. They are also often used as antidepressants for the treatment of major depressive disorders, anxiety and panic disorder. In addition, many drug abuses such as cocaine and methylphenidate have NRI activity, although it is important to mention that NRIs without a combination of dopamine reuptake inhibitor (DRI) properties do not give significant rewards and are therefore considered to have negligible potential abuses. However, norepinephrine has been implicated as acting synergistically with dopamine when action on two neurotransmitters is combined (eg, in the case of NDRI) to produce beneficial effects in the misuse of psychostimulant drugs.
Tricyclic antidepressants
The majority of tricyclic antidepressants (TCAs) act primarily as serotonin-norepinephrine reuptake inhibitors (SNRIs) by blocking serotonin transporters (SERT) and norepinephrine (NET) transporters, respectively, resulting in increased synaptic concentrations of these neurotransmitters. , and therefore increased neurotransmission. In particular, with the only exception of amineptine, TCA has a negligible affinity for dopamine transporters (DAT), and therefore has no efficacy as dopamine reuptake inhibitors (DRIs).
Although TCAs are sometimes prescribed for depressive disorders, they have largely been replaced in clinical use in most of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs ). ). Side effects were found to have similar levels between TCA and SSRI.
Tetracyclic antidepressants
Tetracyclic antidepressants (TeCAs) are the first antidepressant classes introduced in the 1970s. They are named according to their chemical structure, which contains four atomic rings, and are closely related to tricyclic antidepressants (TCA), which contain three atomic rings.
Monoamine oxidase inhibitors
Monoamine oxidase inhibitors (MAOIs) are chemicals that inhibit the activity of the family of monoamine oxidase enzymes. They have a long history of use as a prescribed medication for the treatment of depression. They are very effective at treating atypical depression. They are also used in the treatment of Parkinson's disease and some other disorders.
Due to potentially lethal dietary and drug interactions, monoamine oxidase inhibitors have historically been reserved as the last line of treatment, used only when other classes of antidepressant drugs (eg selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.
MAOI has been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOI appears to be highly effective in the management of bipolar depression according to recent retrospective analyzes. There have been reports of MAOI's efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports.
MAOI can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (because it affects dopaminergic neurons), as well as providing an alternative to migraine prophylaxis. The inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety disorders.
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See a list of antidepressants for other medications that are not specifically characterized.
Adjuncts
Additional treatment is an umbrella term used to describe substances that increase the potency or "boost" antidepressants. They work by influencing variables that are very close to the antidepressants, sometimes affecting the mechanism of action that is completely different. This may be attempted when the treatment of depression has not been successful in the past.
Common types of additional treatment techniques generally fall into the following categories:
- Two or more antidepressants are taken together
- From the same class (affecting the same brain area, often at a much higher level)
- From various classes (affecting some parts of the brain not covered simultaneously by one drug only)
- Antipsychotics combined with antidepressants, especially atypical antipsychotics (Abilify), quetiapine (Seroquel), olanzapine (Zyprexa), and risperidone (Risperdal).
It is not known whether undergoing psychological therapy at the same time by using anti-depressants enhances the anti-depressant effect of the drug.
Additional more common treatments
Lithium has been used to increase antidepressant therapy in those who fail to respond to antidepressants alone. Furthermore, lithium dramatically reduces the risk of suicide in recurrent depression. There is some evidence for the addition of thyroid hormone, triiodothyronine, to patients with normal thyroid function.
Psychopharmacologists also try to add stimulants, in particular, d-amphetamine. However, the use of stimulants in cases of drug-resistant depression is relatively controversial. A review article published in 2007 found that psychostimulants may be effective in drug-resistant depression with concurrent antidepressant therapy, but more definitive conclusions can not be drawn because of substantial deficiencies in the available studies to consider, and the somewhat contradictory nature of their results.
History
Before the 1950s, opioids and amphetamines were commonly used as antidepressants. Its use is then limited due to its addictive nature and side effects. The extract from the herb St. John's wort has been used as a "nerve tonic" to reduce depression.
Isoniazid, iproniazid, and imipramine
In 1951, Irving Selikoff and Edward Robitzek, working at Sea View Hospital in Staten Island, began clinical trials on two new anti-tuberculosis agents developed by Hoffman-LaRoche, isoniazid and iproniazid. Only patients with a poor prognosis were initially treated; However, their condition improved dramatically. Selikoff and Robitzek noted "subtle general stimulation... patients show new strength and indeed this is sometimes presented to introduce disciplinary problems." The promise of a cure for tuberculosis in trials of Sea View Hospital is excitedly discussed in the mainstream press.
In 1952, learning from the side effects of stimulating isoniazid, Cincinnati Lurie's psychiatrist tried it on his patients. The following year, he and Harry Salzer reported that isoniazid improved depression in two-thirds of their patients and coined the term antidepressants to describe the action. A similar incident occurred in Paris, where Jean Delay, the chief psychiatrist at Sainte-Anne Hospital, heard of this effect from her pulmonary colleagues at Cochin Hospital. In 1952 (before Lurie and Salzer), Delays, with residents of Jean-Francois Buisson, reported positive effects of isoniazid in depressed patients. The workings of isoniazid antidepressants remain unclear. It is speculated that the effect is due to diamine oxidase inhibition, coupled with a weak inhibition of monoamine oxidase A.
Selikoff and Robitzek also experimented with other anti-tuberculosis drugs, iproniazid; it shows a greater psychostimulant effect, but the toxicity is more pronounced. Then, Jackson Smith, Gordon Kamman, George Crane, and Frank Ayd, described the psychiatric application of iproniazid. Ernst Zeller found iproniazid as a potent monoamine oxidase inhibitor. Nevertheless, iproniazid remained relatively unclear until Nathan Kline, the influential head of research at Rockland State Hospital, began popularizing it in the medical press and was popular as a "psychic energizer". Roche puts a significant marketing effort behind iproniazid. Its sales grew until it was withdrawn in 1961, due to reports of lethal hepatotoxicity.
The antidepressant effect of tricyclic, a three-ring compound, was first discovered in 1957 by Roland Kuhn in a Swiss mental hospital. Antihistamine derivatives are used to treat surgical shock and then as neuroleptics. Although in 1955 reserpine was shown to be more effective than placebo in reducing anxiety depression, neuroleptics developed as a sedative and antipsychotic.
Seeking to improve the effectiveness of chlorpromazine, Kuhn - together with Geigy Pharmaceutical Company - invented the compound "G 22355", later renamed imipramine. Imipramine has a beneficial effect in patients with depression who exhibit mental and motor retardation. Kuhn describes his new compound as "thymoleptic" "holding the emotion," in contrast to neuroleptics, "holding nerves" in 1955-56. It gradually became established, producing patents and manufacturing in the US in 1951 by HÃÆ'¤fliger and SchinderA.
Second generation antidepressants
Antidepressants became prescription drugs in the 1950s. It is estimated that no more than 50 to 100 people per million suffer from depression as will be treated by these new drugs, and pharmaceutical companies are not enthusiastic in marketing for this small market. Sales until the 1960s remained poor compared to the sale of tranquilizers, which were marketed for various uses. Imipramine remains common and many successors are introduced. The use of monoamine oxidase inhibitors (MAOI) increases after the development and introduction of a "reversible" form that affects only the subtype of MAO-A inhibitor, making it safer to use.
In the 1960s, it was thought that the way tricyclics work is to inhibit norepinephrine reuptake. However, norepinephrine reuptake becomes associated with stimulatory effects. Tricyclics was later thought to affect serotonin as proposed in 1969 by Carlsson and Lindqvist as well as Lapin and Oxenkrug.
The researchers initiated a rational process of drug design to isolate compounds derived from antihistamines that would selectively target these systems. The first patented compound was zimelidine in 1971, while the first released clinically was indalpine. Fluoxetine was approved for commercial use by the US Food and Drug Administration (FDA) in 1988, becoming the first SSRI blockbuster. Fluoxetine was developed at Eli Lilly and Company in the early 1970s by Bryan Molloy, Klaus Schmiegel, David Wong and others. SSRIs are known as "new antidepressants" along with other new drugs such as SNRI and NRI with various selective effects.
St. John Wort was disliked in most countries during the 19th and 20th centuries, except in Germany, where the Hypericum extract was finally licensed, packaged and prescribed. Small-scale efficacy trials were conducted in the 1970s and 1980s, and attention grew in the 1990s following meta-analysis. It remains an OTC supplement in many countries. Research continues to investigate the hyperforin of its active components, and to better understand how it works.
Society and culture
Recipe trends
In the United States, antidepressants are the most commonly prescribed drug in 2013. Of the approximately 16 million "long-term" (more than 24 months) users, about 70 percent are women.
In the UK, the figures reported in 2010 indicate that the number of antidepressants prescribed by the National Health Service (NHS) has nearly doubled over a decade. Further analysis published in 2014 shows that the number of antidepressants disbursed annually in the community increased by 25 million in the 14 years between 1998 and 2012, increasing from 15 million to 40 million. Almost 50% of this increase occurred within four years after the 2008 banking crash, where the time of annual increase in prescriptions increased from 6.7% to 8.5%. These sources also suggest that apart from the recession, other factors that may affect changes in prescribing levels may include: improvements in diagnosis, reduction of stigma around mental health, broader prescribing trends, GP characteristics, geographical location and housing status. Another factor that can contribute to increasing antidepressant consumption is the fact that these drugs are now used for other conditions including social anxiety and post traumatic stress.
Most often specified
United States: The most commonly prescribed antidepressants in the US retail market in 2010 are:
Dutch: In the Netherlands, paroxetine, marketed as Seroxat among generic drugs, is the most prescribed antidepressant, followed by amitriptyline, citalopram and venlafaxine.
Compliance
In 2003, worldwide, 30 to 60% of people did not follow their practitioners' instructions about taking their antidepressants, and by 2013 in the US, about 50% of people did not use their antidepressants as directed by their practitioners..
When people fail to take their antidepressants, there is a greater risk that the drug will not help, the symptoms worsen, that they lose their jobs or are less productive in the workplace, and that the person may be hospitalized. It also increases the cost to care for them.
Social science perspective
In looking at the problem of antidepressant use, some academics have highlighted the need to examine the use of antidepressants and other cross-cultural medical treatments, due to the fact that different cultures prescribe and observe the various manifestations, symptoms, meanings and associations of depression and other medical conditions in their populations. This cross-cultural difference, has been debated, then has implications for the perceived efficacy and use of antidepressants and other strategies in the treatment of depression in these different cultures. In India, antidepressants are widely seen as a tool to combat marginality, promising individuals the ability to reintegrate into society through their use - views and associations not observed in the West.
Environmental impact
Because most of the antidepressant function by inhibiting reuptake of serotonin neurotransmitters, dopamine, and norepinepherine, these drugs can disrupt the level of natural neurotransmitters in other organisms exposed to indirect exposure. Antidepressants fluoxetine and sertraline have been detected in aquatic organisms in the effluent-dominated stream. The presence of antidepressants on the surface of water and aquatic organisms has caused concern because the ecotoxicological effects on aquatic organisms due to fluoxetine exposure have been demonstrated.
Coral reef fish have been shown to modulate aggressive behavior through serotonin. Increasing arotechin levels artificially in crustaceans can reverse the temporary social status and transform subordinates into aggressive and territorial dominant males.
Exposure to fluoxetine has been shown to increase serotonergic activity in fish, which subsequently reduces aggressive behavior. Perinatal exposure to fluoxetine at relevant environmental concentrations has been shown to cause significant modification of the memory process in 1 month old squid. This damage can be detrimental to the squid and reduce their survival. Less than 10% of fluoxetine administered orally is excluded from humans unchanged or as glucuronide.
See also
- Antidepressants in Japan
- Atypical antidepressant
- Atypical depression
- Depression and natural therapy
- The discovery and development of multiple serotonin and norepinephrine reuptake inhibitors
- Listening to Prozac by Peter Kramer
- Anatomy of the Epidemic by Robert Whittaker
- Antidepressants work quickly
- List of antidepressants studied
Category
References
Additional readings
- Stahl SM (1997). Psychopharmacology Antidepressants . Health Information. ISBN 978-1-85317-513-8.
External links
- Media related to Antidepressants in Wikimedia Commons
Source of the article : Wikipedia
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