Selective Serotonin Reuptake Inhibitors (SSRI)

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Although antimuscarinic effects do occur with SSRIs, they are relatively infrequent (and in some cases, negligible). Antimuscarinic effects such as blurred vision, constipation, and urinary retention occur more commonly with tricyclic antidepressants.

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Anxiety, agitation, nervousness, inability to sit still, and insomnia occur most frequently in the first few weeks of starting SSRI treatment. In most cases these effects subside as treatment is continued. It is important to explain this to patients before starting treatment.

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While a beneficial effect may occur within a fortnight, the full effect of an SSRI may take up to six weeks to develop

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All SSRIs inhibit the reuptake of serotonin, but this effect is not confined to the SSRIs. The tricyclic antidepressant clomipramine is a potent serotonin reuptake inhibitor; duloxetine and venlafaxine inhibit the reuptake of both serotonin and noradrenaline.

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Most SSRIs are licensed for administration once daily; fluoxetine and fluvoxamine can be given either as a single dose or in divided doses. There is no reason for giving the second dose in late afternoon—it can be given in the evening or even at bedtime. Generally if the antidepressant is well tolerated, a single daily dose is as effective as taking it in divided doses; once-daily administration might also produce better adherence.

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SSRIs do not generally increase the risk of venous thromboembolism. Drugs that increase platelet aggregation are more likely to cause thromboembolic effects; SSRIs in fact reduce the ability of platelets to aggregate.

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Though very rare, serotonin syndrome typically occurs when an SSRI is taken with another drug that enhances its serotonergic effect or in overdose.

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Sexual dysfunction, including erectile disorders do occur with SSRIs. But it is important to remember that depression is also associated with changes in sexual function.

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Nausea occurs frequently, especially when SSRI treatment is initiated; other gastrointestinal effects associated with SSRIs include vomiting, dyspepsia, and diarrhoea.

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Excessive sweating can occur as a result of SSRI treatment; it can also occur when SSRI treatment is being withdrawn.

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Dry mouth can result from treatment with a variety of antidepressants; for example, the antimuscarinic effects of tricyclic antidepressants include dry mouth.

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Although some features of withdrawal reactions might be different, withdrawal effects can occur with tricyclic antidepressants, serotonin–noradrenaline reuptake inhibitors, as well as SSRIs.

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Though probably more frequent with SSRIs, hyponatraemia (often as a result of syndrome of inappropriate secretion of antidiuretic hormone [SIADH]), can occur with diverse antidepressants.

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Serotonergic mechanism is involved in platelet aggregation and this effect is therefore associated with antidepressants which inhibit serotonin reuptake.

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Insomnia or drowsiness are associated with most antidepressant drugs. Moreover, changes in mood can also affect sleep patterns.

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Giving the antidepressant in the morning may be of benefit if it is associated with insomnia. It is also important to advise the patient about sleep hygiene (establishing regular sleep times; avoiding excessive eating, smoking or alcohol consumption before sleep time; taking regular exercise; and creating an environment conducive to sleep).

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Like diarrhoea and nausea, intensity of sweating may be related to the size of the SSRI dose. Sweating can also occur during drug withdrawal.

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Akathisia—restlessness, agitation, and inability to be still—usually occurs in the first few weeks of starting treatment and usually settles with time. Few patients report sexual side effects spontaneously and the frequency of effects such as decreased libido, impotence, ejaculation disorders and anorgasmia with SSRIs may be underestimated. Taking a history of sexual function before starting SSRI treatment can help with discussion about changes of sexual function during treatment.

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Gastrointestinal disorders are the most frequently reported effects. However, effects such as nausea and diarrhoea generally decrease in intensity and frequency with continued treatment.

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SSRIs are often associated with anorexia and weight loss during initial therapy. However, with continuing treatment, weight can be regained and by the end of treatment there could be an overall weight gain. Weight changes are influenced by the SSRI as well as changes to appetite as a result of improvement in mood.

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This is not true. Withdrawal effects are more common with SSRIs that have a short half-life and withdrawing such SSRIs may require extension of the dose reduction period.

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Withdrawal effects occur with most antidepressants; such reactions are by no means rare with SSRIs.

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SSRI treatment is stopped by decreasing the dose gradually over at least one to two weeks (normally about four weeks and sometimes longer). If withdrawal of an SSRI with a short half-life produces significant reactions, then switching to an SSRI with a long half-life may help with gradual dose reduction.

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Withdrawal effects usually begin within a week (typically 24–72 hours) of stopping SSRI treatment and resolve within three weeks.

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Withdrawal effects can occur after just eight weeks’ of antidepressant use. Discontinuation reactions can also occur after reducing the dose or inadvertently missing to take doses of antidepressant.

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NICE advises that patients at high risk of suicide or those aged under 30 years should be seen one week after starting antidepressant treatment and then frequently until the risk is very much reduced. Other patients started on antidepressants should normally be seen after two weeks and then every two to four weeks for the first three months.

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An antidepressant should be used with caution in patients with a history of mania and it should be discontinued when the patient enters a manic phase of bipolar illness.

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This can be dangerous. To avoid the risk of an interaction, enough time should be allowed for one antidepressant to be washed out of the body before another is introduced. Antidepressants should not normally be given in combination in primary care without the input of a consultant psychiatrist.

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Antidepressants, including SSRIs, carry a small risk of causing hyponatraemia, usually as a result of increased secretion of antidiuretic hormone. Factors such as trauma (especially head trauma) further increase the risk of syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

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These features could spell onset of rare but serious serotonin syndrome, which results from excessive serotonergic effect. It generally follows the concomitant use of two drugs with serotonergic properties (eg SSRI with a 5HT₁ agonist or tramadol) and gives rise to symptoms such as confusion, irritability, agitation, tremor, rigidity, myoclonus, hyperthermia, delirium and coma.