Selective Serotonin Reuptake Inhibitors

GENERAL PRINCIPLES

• The selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for major depressive disorder, anxiety disorders, posttraumatic stress disorder, and other psychiatric conditions.

• The SSRIs have generally supplanted older antidepressants as first-line agents in depression due to their safety profile in therapeutic use and overdose.

• Most SSRIs have similar pharmacologic and toxicologic profiles, with two important exceptions:

î Citalopram is more dangerous in overdose than other SSRIs. Citalopram poisoning tends to produce more cardiotoxicity (QRS and QT prolongation) and seizures than poisoning by other SSRIs.

î Fluoxetine has active metabolites and a very long half-life. Initiation of other serotonergic medications (especially MAO inhibitors—see below) too soon after fluoxetine discontinuation carries a risk of serotonin syndrome (see below).

Pathophysiology

The SSRIs inhibit serotonin reuptake via the SERT transporter on the presynaptic neuron terminal, thus increasing the amount and persistence of serotonin in the synaptic cleft and enhancing serotonergic signaling.

Unlike other antidepressants, the SSRIs have limited effects on any other receptor, channel, or pump.

DIAGNOSIS

Clinical Presentation

• Patients with poisoning due to SSRIs are generally well-appearing and minimally symptomatic. Patients may complain of GI upset and “shakiness.”

• Patients with moderate toxicity may develop mild tachycardia, somnolence, and vomiting.

• Rare patients with severe toxicity may develop dysrhythmias and seizures.

• The development of serotonin syndrome following an acute overdose of a single serotonergic agent is uncommon but possible. Patients with SSRI poisoning should be assessed for evidence of serotonin excess (see below).

Diagnostic Testing

ELECTROCARDIOGRAPHY

• The ECG will typically be unremarkable or demonstrate sinus tachycardia.

• SSRIs may prolong the QT interval in therapeutic use or overdose.

• Citalopram may prolong the QRS interval in significant overdose.

TREATMENT

• The vast majority of patients with SSRI poisoning do not require medical interventions.

• Patients with evidence of significant QT prolongation may benefit from observation on telemetry, supplementation of potassium and magnesium to normal levels, and avoidance of other QT prolonging agents.

î In the uncommon event that torsades de pointes does develop, treat as usual with magnesium and chemical or electrical overdrive pacing.

• Patients with QRS prolongation due to citalopram poisoning should be treated with sodium bicarbonate (see the discussion of TCAs below).

• Treat seizures with benzodiazepines or other directly GABAergic agents.

• Patients with evidence of serotonin excess should be treated as discussed below.