In a study comparing the disposition of intravenously administered diazepam before and after 21 days of dosing with either sertraline (50 to 200 mg/day escalating dose) or placebo, there was a 32% decrease relative to baseline in diazepam clearance for the sertraline hydrochloride group compared to a 19% decrease relative to baseline for the placebo group (p<0.03). There was a 23% increase in Tmax for desmethyldiazepam in the sertraline group compared to a 20% decrease in the placebo group (p<0.03). The clinical significance of these changes is unknown. 

In a placebo-controlled trial in normal volunteers, the administration of two doses of sertraline hydrochloride did not significantly alter steady-state lithium levels or the renal clearance of lithium. 

Nonetheless, at this time, it is recommended that plasma lithium levels be monitored following initiation of sertraline hydrochloride therapy with appropriate adjustments to the lithium dose. 

In a controlled study of a single dose (2 mg) of pimozide, 200 mg sertraline (q.d.) co-administration to steady state was associated with a mean increase in pimozide AUC and Cmax of about 40%, but was not associated with any changes in EKG. Since the highest recommended pimozide dose (10 mg) has not been evaluated in combination with sertraline, the effect on QT interval and PK parameters at doses higher than 2 mg at this time are not known. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide and due to the interaction noted at a low dose of pimozide, concomitant administration of sertraline hydrochloride and pimozide should be contraindicated (see CONTRAINDICATIONS ). 

Results of a placebo-controlled trial in normal volunteers suggest that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonethless, at this time, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline hydrochloride therapy with appropriate adjustments to the phenytoin dose, practiculary in patients with multiple underlying medical conditions and/or those receiving multiple concomitant medications.   
  
The effect of sertraline on valproate levels has not been evaluated in clinical trials. In the absence of such data, it is recommended that plasma valproate levels be monitored following initiation of sertraline therapy with appropriate adjustments to the valproate dose. 

The risk of using sertraline in combination with other CNS active drugs has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of sertraline and such drugs is required. 

There is limited controlled experience regarding the optimal timing of switching from other drugs effective in the treatment of major depressive disorder and premenstrual dysphoric disorder to sertraline. Care and prudent medical judgment should be exercised when switching, particularly from long-acting agents. The duration of an appropriate washout period which should intervene before switching from one selective serotonin reuptake inhibitor (SSRI) to another has not been established.