Table 3.

Clinical management of commonly encountered psychotropic drug-drug interactions.

Drug (Class)	Concomitant offender (ex.)	Mechanism	Clinical management
BZDs (diazepam, alprazolam, midazolam)	Fluvoxamine Nefazodone Indinavir Clarithromycin Azole-antifungals Grapefruit juice	PK: CYP3A4 inhibition	Decrease dose of BZD by 50%. Monitor for excessive CNS effects
	Thiazolidinediones (Pioglitazone, Troglitazone)	PK: CYP3A4 inducer	Consider increase of BZD dose; monitor for efficacy
TCAs (amitriptyline, desipramine)	Paroxetine Fluoxetine	PK: CYP2D6 inhibition	Reduce dose of TCA; consider obtaining TCA drug levels; monitor for CNS and CV effects.
FGA antipsychotics (phenothiazines, haloperidol)	Fluoxetine Fluvoxamine	PK: CYP2D6 inhibition PK: CYP1A2 inhibition	Increased risk for EPS; consider dose reduction of haloperidol.
	Smoking	PK: CYP1A2 induction	Consider increase antipsychotic dose in smokers; consider obtaining therapeutic drug level to aid in monitoring of ADRs
SGA antipsychotics (clozapine, olanzapine, risperidone, quetiapine)	Fluvoxamine Paroxetine, Fluxoxetine Ketoconazole	PK: CYP1A2 inhibition PK: CYP2D6 inhibition PK: CYP3A4 inhibition	Monitor clozapine concentrations; consider SSRI change. Consider dose reduction of risperidone; monitor for EPS. Monitor for excessive CNS effects.
	Smoking	PK: CYP1A2 inducer	Monitor for clozapine or olanzapine efficacy.
	Oral hypoglycemics and anti-lipidemics	PD: Antipsychotic alterations of glucose and lipids	Patients may require addition or increased doses of medications to manage hyperglycemia and/or hyperlipidemia
SSRIs (paroxetine, sertraline, citalopram) and SNRIs (duloxetine)	MAOIs	PD: Decrease metabolism of serotonin	Monitor for serotonin-syndrome risk; consider 14-day washout prior to starting SSRI.
	Triptans	PD: Enhancement of serotonin	Monitor for serotonin-syndrome risk; consider avoiding combination
	Hydrocodone	PK: CYP2D6 inhibition	Reduction of analgesic effect, due to CYP inhibition. May require increased doses of analgesic or switch to non-CYP2D6 metabolized analgesic
Lithium	ACE inhibitors NSAIDs, thiazides	PK: Inhibition of renal clearance	Monitor for elevated Li+ levels; consider dose reduction
HMG-CoA reductase inhibitors (simvastatin)	Nefazodone Fluvoxamine	PK: CYP3A4 inhibition	Monitor for myopathy; consider removal of offending inhibitor
Warfarin (s-isomer, active)	Carbamazepine	PK: CYP2C9 inducer	Monitor INR
	Fluoxetine, valproic acid	PK: CYP2C9 inhibitor	Monitor INR, PT.
Calcium channel blockers (verapamil, nicardipine, nimodipine)	Nefazodone, fluvoxamine	PK: CYP3A4 inhibitor	Consider decrease of CCB dose by 50%.
COX-2 inhibitors (celecoxib)	Paroxetine	PK: CYP2D6 inhibitor	Monitor therapy
Antihyperglycemic (glimepiride)	Fluvoxamine	PK: CYP1A2 inhibitor	Monitor glycemic status
Clopidogrel	Fluvoxamine Nefazodone	PK: CYP1A2 inhibition PK: CYP3A4 inhibition	May weaken anti-platelet effects of clopidogrel; monitor therapy.