Antidepressant
Antidepressants, also known in the past as psychic energizers, are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexual dysfunction, and emotional blunting. There is an increased risk of suicidal thinking and behavior when taken by children, adolescents, and young adults. Discontinuation syndrome, which resembles recurrent depression in the case of the SSRI class, may occur after stopping the intake of any antidepressant, having effects which may be permanent and irreversible. Tapering off medications gradually is shown to reduce the risk of withdrawal complications.
The effectiveness of antidepressants for treating depression in adults has strong support, though studies also highlight potential risks and limitations. In children and adolescents, evidence of efficacy is more limited, despite a marked increase in antidepressant prescriptions for these age groups since the 2000s. A 2018 meta-analysis reported that the 21 most commonly prescribed antidepressants were found in all studies to be more effective than placebos for the short-term treatment of major depressive disorder in adults. However, other research suggests that some benefits may be attributable to the placebo effect. Response to antidepressants is highly variable, and medications that are effective for certain patients may have no effect or a negative effect for others. Research into the factors that influence individual responses to antidepressants is ongoing.
Medical uses
Antidepressants are prescribed to treat major depressive disorder, anxiety disorders, chronic pain, and some addictions. Antidepressants are often used in combination with one another.Despite its longstanding prominence in pharmaceutical advertising, the idea that low serotonin levels cause depression is not supported by scientific evidence. Proponents of the monoamine hypothesis of depression recommend choosing an antidepressant which impacts the most prominent symptoms. Under this practice, for example, a person with MDD who is also anxious or irritable would be treated with selective serotonin reuptake inhibitors or norepinephrine reuptake inhibitors, while a person suffering from loss of energy and enjoyment of life would take a norepinephrine–dopamine reuptake inhibitor.
Major depressive disorder
The UK National Institute for Health and Care Excellence '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". The guidelines recommended that antidepressant treatment be considered:- For people with a history of moderate or severe depression.
- For people with mild depression that has been present for an extended period.
- As a first-line treatment for moderate to severe depression.
- As a second-line treatment for mild depression that persists after other interventions.
American Psychiatric Association treatment guidelines recommend that initial treatment be individually tailored based on factors including the severity of symptoms, co-existing disorders, prior treatment experience, and the person's preference. Options may include antidepressants, psychotherapy, electroconvulsive therapy, transcranial magnetic stimulation, or light therapy. The APA recommends antidepressant medication as an initial treatment choice in people with mild, moderate, or severe major depression, and that should be given to all people with severe depression unless ECT is planned.
Reviews of antidepressants generally find that they benefit adults with depression. On the other hand, some contend that most studies on antidepressant medication are confounded by several biases: the lack of an active placebo, which means that many people in the placebo arm of a double-blind study may deduce that they are not getting any true treatment, thus destroying double-blindness; a short follow up after termination of treatment; non-systematic recording of adverse effects; very strict exclusion criteria in samples of patients; studies being paid for by the industry; selective publication of results. This means that the small beneficial effects that are found may not be statistically significant.
Among the 21 most commonly prescribed antidepressants, the most effective and well-tolerated are escitalopram, paroxetine, sertraline, agomelatine, and mirtazapine. For children and adolescents with moderate to severe depressive disorder, some evidence suggests fluoxetine is the best treatment, but more research is needed to be certain. Sertraline, escitalopram, and duloxetine may also help reduce symptoms.
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. 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. Quality of life as an outcome measure is often selectively reported in trials of antidepressants.
Anxiety disorders
For children and adolescents, fluvoxamine and escitalopram are effective in treating a range of anxiety disorders. Fluoxetine, sertraline, and paroxetine can also help with managing various forms of anxiety in children and adolescents.Meta-analyses of published and unpublished trials have found that antidepressants have a placebo-subtracted effect size in the treatment of anxiety disorders of around 0.3, which equates to a small improvement and is roughly the same magnitude of benefit as their effectiveness in the treatment of depression. The effect size for improvement with placebo in trials of antidepressants for anxiety disorders is approximately 1.0, which is a large improvement in terms of effect size definitions. In relation to this, most of the benefit of antidepressants for anxiety disorders is attributable to placebo responses rather than to the effects of the antidepressants themselves.
Generalized anxiety disorder
Antidepressants are recommended by the National Institute for Health and Care Excellence for the treatment of generalized anxiety disorder that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder in which the central feature is excessively worrying about numerous events. Key symptoms include excessive anxiety about events and issues going on around them and difficulty controlling worrisome thoughts that persists for at least 6 months.Antidepressants provide a modest to moderate reduction in anxiety in GAD. The efficacy of different antidepressants is similar.
Social anxiety disorder
Some antidepressants are used as a treatment for social anxiety disorder, but their efficacy is not entirely convincing, as only a small proportion of antidepressants showed some effectiveness for this condition. Paroxetine was the first drug to be FDA-approved for this disorder. Its efficacy is considered beneficial, although not everyone responds favorably to the drug. Sertraline and fluvoxamine extended-release were later approved for it as well, while escitalopram is used off-label with acceptable efficiency. However, there is not enough evidence to support citalopram for treating social anxiety disorder, and fluoxetine was no better than a placebo in clinical trials. Vortioxetine may be of benefit. SSRIs are used as a first-line treatment for social anxiety, but they do not work for everyone. 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., it is unclear if duloxetine and desvenlafaxine can provide benefits for people with social anxiety. However, another class of antidepressants called MAOIs are considered effective for social anxiety, but they come with many unwanted side effects and are rarely used. Phenelzine was shown to be a good treatment option, but its use is limited by dietary restrictions. Moclobemide is a RIMA and showed mixed results, but still received approval in some European countries for social anxiety disorder. TCA antidepressants, such as clomipramine and imipramine, are not considered effective for this anxiety disorder in particular. This leaves out SSRIs such as paroxetine, sertraline, and fluvoxamine CR as acceptable and tolerated treatment options for this disorder.Obsessive–compulsive disorder
SSRIs are a second-line treatment for adult obsessive–compulsive disorder with mild functional impairment, and a first-line treatment for those with moderate or severe impairment.In children, SSRIs are considered as a second-line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects. Sertraline and fluoxetine are effective in treating OCD for children and adolescents.
Clomipramine, a TCA drug, is considered effective and useful for OCD. However, it is used as a second-line treatment because it is less well-tolerated than SSRIs. Despite this, it has not shown superiority to fluvoxamine in trials. All SSRIs can be used effectively for OCD. SNRI use may also be attempted, though no SNRIs have been approved for the treatment of OCD. Despite these treatment options, many patients remain symptomatic after initiating the medication, and less than half achieve remission.
Placebo responses are a large component of the benefit of antidepressants in the treatment of depression and anxiety. However, placebo responses with antidepressants are lower in magnitude in the treatment of OCD compared to depression and anxiety. A 2019 meta-analysis found placebo improvement effect sizes of about 1.2 for depression, 1.0 for anxiety disorders, and 0.6 for OCD with antidepressants.