What is the most effective SSRI for depression?

Antidepressants are a type of medicine used to treat clinical depression.

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Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-noradrenaline reuptake inhibitors (SNRIs)
Noradrenaline and specific serotonergic antidepressants (NASSAs)
Tricyclic antidepressants (TCAs)
Serotonin antagonists and reuptake inhibitors (SARIs)
Monoamine oxidase inhibitors (MAOIs)

They can also be used to treat a number of other conditions, including:

Antidepressants are also sometimes used to treat people with long-term (chronic) pain.

Read more about when antidepressants are used.

It's not known exactly how antidepressants work.

It's thought they work by increasing levels of chemicals in the brain called neurotransmitters. Certain neurotransmitters, such as serotonin and noradrenaline, are linked to mood and emotion.

Neurotransmitters may also affect pain signals sent by nerves, which may explain why some antidepressants can help relieve long-term pain.

While antidepressants can treat the symptoms of depression, they do not always address its causes. This is why they're usually used in combination with therapy to treat more severe depression or other mental health conditions.

Research suggests that antidepressants can be helpful for people with moderate or severe depression.

They're not usually recommended for mild depression, unless other treatments like talking therapy have not helped.

Antidepressants are usually taken in tablet form. When they're prescribed, you'll start on the lowest possible dose thought necessary to improve your symptoms.

Antidepressants usually need to be taken for 1 or 2 weeks (without missing a dose) before the benefit starts to be felt. It's important not to stop taking them if you get some mild side effects early on, as these effects usually wear off quickly.

If you take an antidepressant for 4 weeks without feeling any benefit, speak to your GP or mental health specialist. They may recommend increasing your dose or trying a different medicine.

A course of treatment usually lasts for at least 6 months after you start to feel better. Some people with recurrent depression may be advised to take them indefinitely.

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs are the most widely prescribed type of antidepressants. They're usually preferred over other antidepressants, as they cause fewer side effects. An overdose is also less likely to be serious.

Fluoxetine is probably the best known SSRI (sold under the brand name Prozac). Other SSRIs include citalopram (Cipramil), escitalopram (Cipralex), paroxetine (Seroxat) and sertraline (Lustral).

Serotonin-noradrenaline reuptake inhibitors (SNRIs)

SNRIs are similar to SSRIs. They were designed to be a more effective antidepressant than SSRIs. However, the evidence that SNRIs are more effective in treating depression is uncertain. It seems that some people respond better to SSRIs, while others respond better to SNRIs.

Examples of SNRIs include duloxetine (Cymbalta and Yentreve) and venlafaxine (Efexor).

Noradrenaline and specific serotonergic antidepressants (NASSAs)

NASSAs may be effective for some people who are unable to take SSRIs. The side effects of NASSAs are similar to those of SSRIs, but they're thought to cause fewer sexual problems. However, they may also cause more drowsiness at first.

The main NASSA prescribed in the UK is mirtazapine (Zispin).

Tricyclic antidepressants (TCAs)

TCAs are an older type of antidepressant. They're no longer usually recommended as the first treatment for depression because they can be more dangerous if an overdose is taken. They also cause more unpleasant side effects than SSRIs and SNRIs.

Exceptions are sometimes made for people with severe depression that fail to respond to other treatments. TCAs may also be recommended for other mental health conditions, such as OCD and bipolar disorder.

Examples of TCAs include amitriptyline, clomipramine, dosulepin, imipramine, lofepramine and nortriptyline.

Some types of TCAs, such as amitriptyline, can also be used to treat chronic nerve pain.

Serotonin antagonists and reuptake inhibitors (SARIs)

SARIs are not usually the first choice of antidepressant, but they may be prescribed if other antidepressants have not worked or have caused side effects.

The main SARI prescribed in the UK is trazodone (Molipaxin).

Monoamine oxidase inhibitors (MAOIs)

MAOIs are an older type of antidepressant that are rarely used nowadays.

They can cause potentially serious side effects so should only be prescribed by a specialist doctor.

Examples of MAOIs include tranylcypromine, phenelzine and isocarboxazid.

Other treatments for depression include talking therapies such as cognitive behavioural therapy (CBT).

People with moderate to severe depression are usually treated using a combination of antidepressants and CBT. Antidepressants work quickly in reducing symptoms, whereas CBT takes time to deal with causes of depression and ways of overcoming it.

Regular exercise has also been shown to be useful for those with mild depression.

Read more about alternatives to antidepressants.

The Yellow Card Scheme allows you to report suspected side effects from any type of medicine you're taking. It's run by a medicines safety watchdog called the Medicines and Healthcare products Regulatory Agency (MHRA).

See the Yellow Card Scheme website for more information.

Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.

We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.

We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72–0·97) and fluoxetine (0·88, 0·80–0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01–1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.

All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.

National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.