Sertraline arrhythmia with

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Use with CYP450 3A4 inhibitors (e.g., drugs such as fluoxetine, sertraline, fluvoxamine, and nefazodone foods such as grapefruit juice) can raise pimozide levels and increase the risks of dangerous arrhythmias... 

Pimozide levels are expected to rise when used with fluoxetine, fluvoxamine, paroxetine, or sertraline, which would increase the risk of potentially fatal torsade de pointes arrhythmias. The use of SSRIs and pimozide has also led to extrapyramidal adverse effects, oculogyric crises and sedation in rare cases. 

Evidence is limited, however the interaction is potentially severe as raised pimozide levels can cause torsade de pointes arrhythmias, which can be fatal. The manufacturers of pimozide contraindicate its use with SSRIs, and in the UK they specifically name sertraline, paroxetine, and citalo-pram which has been seen to cause QT prolongation with pimozide, and its isomer, escitalopram. The US manufacturers additionally contraindicate fluvoxamine." Neither manufacturer mentions fluoxetine (except with regard to the possibility of additive bradycardia"), but as it is known to have greater effects on CYP2D6 than either sertraline or citalopram, it would seem prudent to also consider it as contraindicated. 

The FDA warning on citalopram remains controversial. A retrospective cohort study [34 ], using Veterans Health Administration data collected between 2004 and 2009 from depressed patients who either received a prescription for citalopram (n=6,18,450) or a comparison medication, sertraline (n=3,65,898), found citalopram daily doses of above 40 mg were not associated with a higher risk of ventricular arrhythmia, or cardiac or noncardiac death. In fact, the authors found that citalopram dosages above 40 mg per day were associated with a statistically significantly reduced risk of ventricular arrhythmia, all-cause mortality and noncardiac mortality compared to doses of 20 mg or less. 

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