Antidepressant
[1] Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia,[2] sexual dysfunction,[3][4][5][6][7] and emotional blunting.
[28] The UK National Institute for Health and Care Excellence (NICE)'s 2022 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, "unless that is the person's preference".
[38] A 2023 systematic review and meta-analysis of randomized controlled trials of antidepressants for major depressive disorder found that the medications provided only small or doubtful benefits in terms of quality of life.
[39] Likewise, a 2022 systematic review and meta-analysis of randomized controlled trials of antidepressants for major depressive disorder in children and adolescents found small improvements in quality of life.
[44][45] Antidepressants are recommended by the National Institute for Health and Care 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.
One alternative would be venlafaxine, an SNRI, which has shown benefits for social phobia in five clinical trials against a placebo, while the other SNRIs are not considered particularly useful for this disorder as many of them did not undergo testing for it.
Those from the American Psychiatric Association (APA) note that SSRIs confer no advantage regarding weight gain, but may be used for the treatment of co-existing depressive, anxiety, or obsessive–compulsive disorders.
[64] 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".
[72] Certain antidepressants acting as serotonin 5-HT2A receptor antagonists, such as trazodone and mirtazapine, have been used as hallucinogen antidotes or "trip killers" to block the effects of serotonergic psychedelics like psilocybin and lysergic acid diethylamide (LSD).
[79] According to data from the Centers for Disease Control and Prevention, less than one-third of Americans taking one antidepressant medication have seen a mental health professional in the previous year.
[89] Assessments of antidepressants using alternative, more sensitive scales, such as the MADRS, do not result in marked difference from the HDRS and likewise only find a marginal clinical benefit.
[100][97][101] Ghostwriting of antidepressant trials is widespread, a practice in which prominent researchers, or so-called key opinion leaders, attach their names to studies actually written by pharmaceutical company employees or consultants.
A 2006 meta-analysis review found wide variation in the findings of prior studies: for people who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug.
If taken with foods that contain very high levels of tyramine (e.g., mature cheese, cured meats, or yeast extracts), they may cause a potentially lethal hypertensive crisis.
The primary advantage of RIMAs is that they do not require the person to follow a special diet while being purportedly effective as SSRIs and tricyclics in treating depressive disorders.
[130] Tricyclics and SSRI can cause the so-called drug-induced QT prolongation, especially in older adults;[131] this condition can degenerate into a specific type of abnormal heart rhythm called Torsades de points, which can potentially lead to sudden cardiac arrest.
[181][182] The antihistaminic properties of certain TCA- and TeCA-class antidepressants have been shown to contribute to the common side effects of increased appetite and weight gain associated with these classes of medication.
[183] A 2012 review found that SSRIs along with tricyclic antidepressants were associated with a significant increase in the risk of osteoporotic fractures, peaking in the months after initiation, and moving back towards baseline during the year after treatment was stopped.
[203][204][205][206] In 2022, a major systematic umbrella review by Joanna Moncrieff and colleagues showed that the serotonin theory of depression was not supported by evidence from a wide variety of areas.
[97][90][214][84][85] The difference between antidepressants and placebo corresponds to an effect size (SMD) of about 0.3, which in turn equates to about a 2- to 3-point additional improvement on the 0–52-point (HRSD) and 0–60-point (MADRS) depression rating scales used in trials.
[44][221][222][223][101] However, another academic, Michael P. Hengartner, has argued and presented evidence that spontaneous remission and regression to the mean might actually account for most of the improvement in depression scores with antidepressants, and that the substantial placebo effect observed in clinical trials might largely be a methodological artifact.
[266][267] A review article published in 2007 found psychostimulants may be effective in treatment-resistant depression with concomitant antidepressant therapy, but a more certain conclusion could not be drawn due to substantial deficiencies in the studies available for consideration, and the somewhat contradictory nature of their results.
[270] St John's wort fell out of favor in most countries through the 19th and 20th centuries, except in Germany, where Hypericum extracts were eventually licensed, packaged, and prescribed.
[273][274] In 1951, Irving Selikoff and Edward H. Robitzek, working out of Sea View Hospital on Staten Island, began clinical trials on two new anti-tuberculosis agents developed by Hoffman-LaRoche, isoniazid, and iproniazid.
Selikoff and Robitzek noted "a subtle general stimulation ... the patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems.
[medical citation needed] Attempting to improve the effectiveness of chlorpromazine, Kuhn — in conjunction with the Geigy Pharmaceutical Company — discovered the compound "G 22355", later renamed imipramine.
[288] Esketamine (brand name Spravato), the first rapid-acting antidepressant to be approved for clinical treatment of depression, was introduced for this indication in March 2019 in the United States.
[42][298] Among the suggested possible reasons why GPs are not following the guidelines are the difficulties of accessing talking therapies, long waiting lists, and the urgency of treatment.
[308][309] In India, antidepressants are largely seen as tools to combat marginality, promising the individual the ability to reintegrate into society through their use—a view and association not observed in the West.
[314] Artificially increasing serotonin levels in crustaceans can temporarily reverse social status and turn subordinates into aggressive and territorial dominant males.
