Antidepressants

In: Management

The effects of prescription antidepressants are somewhat superior to those of psychotherapy, especially in cases of chronic major depression, although in short-term trials more patients—especially those with less serious forms of depression—cease medication than cease psychotherapy, most likely due to adverse effects from the medication and to patients' preferences for psychological therapies over pharmacological treatments.

To find the most effective antidepressant medication with minimal side effects, the dosages can be adjusted, and if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered range from 50–75%, and it can take at least six to eight weeks from the start of medication to remission, when the patient is back to their normal self. Antidepressant medication treatment is usually continued for 16 to 20 weeks after remission, to minimize the chance of recurrence, and even up to one year of continuation is recommended. People with chronic depression may need to take medication indefinitely to avoid relapse.

Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, escitalopram, fluoxetine, paroxetine, and citalopram are the primary medications prescribed owing to their effectiveness, relatively mild side effects, and because they are less toxic in overdose than other antidepressants. Patients who do not respond to one SSRI can be switched to another antidepressant, and this results in improvement in almost 50% of cases. Another option is to switch to the atypical antidepressant bupropion. Venlafaxine, an antidepressant with a different mechanism of action, may be modestly more effective than SSRIs. However, venlafaxine is not recommended in the UK as a first-line treatment because of evidence suggesting its risks may outweigh benefits, and it is specifically discouraged in children and adolescents. For adolescent depression, fluoxetine and escitalopram are the two recommended choices. Antidepressants have not been found to be beneficial in children. Any antidepressant can cause low serum sodium levels (also called hyponatremia); nevertheless, it has been reported more often with SSRIs. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating antidepressant mirtazapine can be used in such cases.

Monoamine oxidase inhibitors, an older class of antidepressants, have been plagued by potentially life-threatening dietary and drug interactions. They are still used only rarely, although newer and better tolerated agents of this class have been developed.

The terms "refractory depression" and "treatment-resistant depression" are used to describe cases that do not respond to adequate courses of at least two antidepressants. In many major studies, only about 35% of patients respond well to medical treatment. It may be difficult for a doctor to decide when someone has treatment-resistant depression or whether the problem is due to coexisting disorders, which are common among patients with major depression.

A team of psychologists from multiple American universities found that antidepressant drugs hardly have better effects than a placebo in cases of mild or moderate depression. The study focused on paroxetine and imipramine.

Pharmacological augmentation

A medication with a different mode of action may be added to bolster the effect of an antidepressant in cases of treatment resistance. Medication with lithium salts has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, lithium dramatically decreases the suicide risk in recurrent depression. Addition of a thyroid hormone, triiodothyronine may work as well as lithium, even in patients with normal thyroid function. Addition of atypical antipsychotics when the patient has not responded to an antidepressant is also known to increase the effectiveness of antidepressant drugs, albeit offset by increased side effects.

Comparative efficacy of medication and psychotherapy

Two recent meta-analyses of clinical trial results submitted to the FDA concluded that antidepressants are statistically superior to placebo but their overall effect is low-to-moderate. In that respect they often did not exceed the National Institute for Health and Clinical Excellence criteria for a "clinically significant" effect. In particular, the effect size was very small for moderate depression but increased with severity, reaching "clinical significance" for very severe depression. These results were consistent with the earlier clinical studies in which only patients with severe depression benefited from either psychotherapy or treatment with an antidepressant, imipramine, more than from the placebo treatment. Despite obtaining similar results, the authors argued about their interpretation. One author concluded that there "seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide benefit." The other author agreed that "antidepressant 'glass' is far from full" but disagreed "that it is completely empty". He pointed out that the first-line alternative to medication is psychotherapy, which does not have superior efficacy.

One interpretation of the research is that antidepressants in general are as effective as psychotherapy for major depression, and that this conclusion holds true for both severe and mild forms of MDD. In contrast, medication gives better results for dysthymia. The subgroup of SSRIs may be slightly more efficacious than psychotherapy. On the other hand, significantly more patients drop off from the antidepressant treatment than from psychotherapy, likely because of the side effects of antidepressants. Successful psychotherapy appears to prevent the recurrence of depression even after it has been terminated or replaced by occasional "booster" sessions. The same degree of prevention can be achieved by continuing antidepressant treatment. However, another argument is that medication and psychotherapy are two very different things and comparisons are not scientifically valid. Psychotherapy involves addressing and understanding the meaning behind emotions, whilst medication involves regulating those emotions through biochemical means. In many cases, both approaches may be necessary either in combination or in sequence.

Antidepressants and suicidality

For children, adolescents, and in some studies also for young adults between 18–24 years old, there is a higher risk of both suicidal ideations and suicidal behavior in those treated with SSRIs. For adults, it is unclear whether or not SSRIs affect the risk of suicidality. One review found no connection between SSRIs and the risk of suicide; other studies found an increase in suicide attempts by those who use SSRIs as compared to placebo; and yet other studies found that the widespread use of antidepressants in the new “SSRI-era” appeared to have led to a highly significant decline in suicide rates in most countries with traditionally high baseline suicide rates.

A black box warning was introduced in the United States in 2007 on SSRI and other antidepressant medications due to increased risk of suicide in patients younger than 24 years old. Similar precautionary notice revisions were implemented by the Japanese Ministry of Health.