Psychiatric Morbidity and Other Factors Affecting Treatment Adherence in Pulmonary Tuberculosis Patients

Table 6

Clinically significant drug-drug interactions involving TB medications and psychiatric medications.

TB medications	Psychiatric medications	Interactions	References
Isoniazid, in therapeutic dose		Was found to inhibit markedly plasma, but not platelet, MAO.	[149]
Drug that inhibits monoamine oxidase	SSRIs or TCAs.	Is contraindicated because of the potential to induce serotonin syndrome	[150]
		No reports of serotonin syndrome induced by combining SSRIs and isoniazid are published.	[151]
Isoniazid	Phenytoin and carbamazepine; selected benzodiazepines (valium and others); Valproate; Haldol.	Isoniazid can cause increased phenytoin and carbamazepine serum concentrations and toxicity.; Isoniazid inhibits metabolism of selected benzodiazepines.; Inhibition of monoamine oxidase and histaminase by Isoniazid can cause significant drug-food interactions.; isoniazid has a biphasic effect of inhibition-induction on one cytochrome P450 isozyme, CYP2E1 and increases hepatic and CNS valproate toxicity and haldol toxicity.	[152]; [153]
Isoniazid	2 patients who received isoniazid in conjunction with antidepressants. The first patient was prescribed sertraline (150 mg/day) in combination with isoniazid (300 mg/day). The second patient received nefazodone (400 mg/day) and buspirone (10 mg/day) in conjunction with isoniazid (300 mg/day).	None of patients reported adverse effects.	[150]
Isoniazid	SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline).	Are metabolized by similar mechanisms.; Hepatic cytochrome P450 (CYP) enzymes are largely responsible for metabolism of isoniazid, citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. While it has not been definitively established which isoenzymes are implicated in the metabolism of isoniazid, CYP2E1, CYP1A2, CYP2C9, CYP2C19, and CYP3A are inhibited to varying degrees by isoniazid.; CYP2C19 and CYP3A were inhibited potently by isoniazid in a concentration-dependent manner. Both enzymes were inhibited approximately 40% by doses in the therapeutic range. Isoniazid induced competitive inhibition of CYP2D6 and weak noncompetitive inhibition of CYP2E1.	[154]
Isoniazid	Paroxetine is metabolized primarily by CYP2D6.	CYP2D6 is affected negligibly by isoniazid. The potential for drug interactions would appear to be minimal.	[24]
Isoniazid	Citalopram appears to be metabolized primarily by CYP2C19 and/or CYP3A4.	CYP2C19 and/or CYP3A4 are inhibited by isoniazid. It might not be the best choice for a patient taking isoniazid.	[155–157]
Isoniazid	Fluvoxamine is known to inhibit CYP1A2, CYP2C19, and possibly CYP3A3/4.	CYP1A2, CYP2C19, and CYP3A3/4 are inhibited by isoniazid	[158–160]
Isoniazid	Fluoxetine inhibits CYP2D6 and probably CYP2C9/10 significantly, and CYP3A3/4 and CYP2C19 to a lesser extent metabolite of fluoxetine, norfluoxetine inhibits CYP3A3/4 and has a half-life of 7 to 15 days.	CYP3A3/4 is inhibited by isoniazid; increased potential for drug interactions.	[161–163]
Isoniazid	Sertraline probably inhibits CYP3A.	CYP3A is implicated in the metabolism of isoniazid.	[161, 162]
Rifampin	Antidepressants, haldol, quetiapine, methadone,; phenytoin, valproic acid, lamotrigine, buspirone,; benzodiazepines (diazepam, tiazolam), and zolpidem.	Reduces their levels.	[164]
Rifampin	Nortriptyline	A case report; Higher than expected doses of nortriptyline were required to obtain a therapeutic drug level while the patient was receiving rifampin.	[165]