The most effective antidepressants for adults

The most effective antidepressants for adults

The most effective antidepressants for adults

The most effective antidepressants for adults

A major review has revealed the most effective antidepressants for adults. Adults who suffer from moderate to severe depression can benefit from antidepressants. Five antidepressants appear to be more effective and tolerable than others.

In short-term trials measuring response to treatment, all 21 drugs studied performed better than placebo, according to a large review of 522 antidepressant trials. The effectiveness, on the other hand, varied greatly.

Researchers ranked drugs by effectiveness and acceptability after eight weeks of treatment. Several drugs were more effective and were stopped by fewer people than others:

  • escitalopram
  • paroxetine
  • sertraline
  • agomelatine
  • mirtazapine.

The review provides new evidence that may assist people in deciding which antidepressant to use first in the treatment of moderate to severe depression. It did not, however, compare antidepressants to other treatments, such as cognitive behavioral therapy, or treatments in combination. Despite some reservations about items not reported by individual trials, this review is likely to be trustworthy. It is extensive, included only placebo controlled double blind trials and searched successfully for unpublished trials.

Antidepressants are effective to treat moderate to severe depression in adults. Five antidepressants appear more effective and better tolerated than others.

A major review of 522 antidepressant trials found that all of the 21 drugs studied performed better than placebo, in short-term trials measuring response to treatment. However, effectiveness varied widely.

Why was this study needed?

Depression is a common condition that affects one out of every ten adults at some point in their lives. Antidepressants, as well as psychological interventions such as cognitive behavioral or interpersonal therapy, are commonly prescribed in primary and secondary care. Although NICE recommends a selective sertraline antidepressant, there is conflicting evidence to guide which antidepressants should be prescribed first-line.

In recent years, there has been some debate about the efficacy of antidepressants. Their mechanism of action is unknown, and the improvement in mood is usually modest. According to one 2008 meta-analysis, antidepressants provided little benefit over placebo for mild to moderate depression.
This new study went to great lengths to find unpublished studies as well as additional data from published studies.

What did this study do?

This systematic review and network meta-analysis compared 21 antidepressants to placebo or to each other, both within trials and across trials. They included 522 double-blind randomized controlled trials involving 116,477 adults suffering from moderate to severe depression.

More than 100 trials were previously unpublished. As well as publication databases, international trial registers and drug approval websites, the researchers had contacted all pharmaceutical companies marketing antidepressants to ask for unpublished studies.

The antidepressants were compared for effectiveness (at least 50% improvement in symptoms) and acceptability (assessed as drop-out rate). They found 380 trials at possible risk of bias due mainly to lack of reporting of randomisation methods, and 46 at high risk. However, the trials were all placebo controlled.

What did it find?

All 21 antidepressants were more likely to produce a treatment response after eight weeks treatment than a placebo. The most effective antidepressant compared to placebo was the tricyclic antidepressant amitriptyline, which increased the chances of treatment response more than two-fold (odds ratio [OR] 2.13, 95% credible interval [CrI] 1.89 to 2.41). The least effective was the serotonin and noradrenaline reuptake inhibitor reboxetine, which increased treatment response by 37% (OR 1.37, 95% CrI 1.16 to 1.63).

Drop-out rates by eight weeks of treatment were similar to placebo for the majority of antidepressants. People were 30% more likely to stop taking the tricyclic clomipramine than placebo (OR 1.30, 95% CrI 1.01 to 1.68) and slightly less likely to stop taking agomelatine (an “atypical” antidepressant) or the SSRI fluoxetine (OR for agomelatine 0.84, 95% CrI 0.72 to 0.97; OR for fluoxetine 0.88, 95% CrI 0.8 to 0.96).

In head-to-head comparisons between the drugs, five were identified as having a combination of better effectiveness and lower drop-out rates, compared to others: the SSRIs escitalopram, paroxetine and sertraline, and atypicals agomelatine and mirtazapine. Reboxetine (atypical), trazodone (similar to a tricyclic) and fluvoxamine (SSRI) were identified as having lower effectiveness and higher drop-out rates.

Though absolute effect sizes were not reported in the results, the researchers described the effect sizes as “modest”. However, they also said that “non-response to treatment will occur.”

What does current guidance say on this issue?

According to the NICE 2009 depression guideline, people with moderate to severe depression should be given an antidepressant as well as psychological therapy such as cognitive behavioral therapy or interpersonal therapy. According to the document, the antidepressant prescribed “should normally be an SSRI in a generic form because SSRIs are equally effective as other antidepressants and have a favorable risk-benefit ratio.”

The guideline warns that venlafaxine is more associated with risk of death from overdose than other SSRIs, while “tricyclic antidepressants, except for lofepramine, are associated with the greatest risk in overdose.”

What are the implications?

The findings will be of interest to general practitioners and psychiatrists.  Both must decide on the best initial treatment for adults suffering from moderate to severe depression. The comparative data may aid doctors in selecting drugs with higher efficacy and fewer side effects.

However, treatment choice will be guided by an individual patient’s circumstances and preferences. The meta-analysis was unable to look at the potentially different effects of treatment on subgroups based on age, sex, the severity of symptoms or duration of illness.

The review did not consider combined drug and psychological treatments.  This as recommended by NICE for moderate to severe depression, or long-term effects which limit its applicability.

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