pyrimidinones and Bipolar-Disorder

To describe a case of exacerbated mania potentially related to an interaction between lopinavir/ritonavir and valproic acid (VPA) and propose a mechanism of action for this interaction.. A 30-year-old man with bipolar disorder and HIV initiated treatment with lopinavir/ritonavir, zidovudine, and lamivudine. Prior to beginning therapy with these antiretrovirals, he was receiving VPA 250 mg 3 times daily, with his most recent VPA concentration measured at 495 micromol/L. Twenty-one days after starting antiretroviral treatment, he became increasingly manic. His VPA concentration at admission was 238 micromol/L, a 48% decrease. The daily VPA dose was increased to 1500 mg, and olanzapine was introduced. The VPA concentration following this dose escalation was 392 micromol/L, and the patient improved clinically.. Fifty percent of VPA is metabolized by glucuronidation, 40% undergoes mitochondrial beta-oxidation, and less than 10% is eliminated by the cytochrome P450 isoenzymes. Ritonavir can induce glucuronidation of several medications including ethinyl estradiol, levothyroxine, and lamotrigine. We believe that ritonavir-mediated induction of VPA glucuronidation resulted in a decrease in VPA concentrations and efficacy. An objective causality assessment suggested that the increased mania was probably related to the decrease in VPA concentration and that a possible interaction exists between lopinavir/ritonavir and VPA.. A potential interaction exists between VPA and all ritonavir-boosted antiretroviral regimens. Clinicians should monitor patients closely for a decreased VPA effect when these medications are given concomitantly.

Topics: Adult; Antiretroviral Therapy, Highly Active; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Interactions; Hepatitis C; HIV Infections; Humans; Lopinavir; Male; Pyrimidinones; Ritonavir; Valproic Acid

To examine the effects of treatment with valproate on brain 5-HT2A receptors in acute manic patients using positron emission tomography (PET) and [18F]-setoperone.. Patients with DSM-IV bipolar I disorder-manic episode were recruited. Patients were drug free or drug naïve at the time of baseline PET scan. All patients were treated with valproate and one patient received lithium in addition to valproate for 3-5 weeks following which they had a post-treatment PET scan. The effect of treatment on brain 5-HT2A receptor binding was determined using statistical parametric mapping (SPM) and region of interest (ROI) analyses. Of the 12 manic patients recruited, seven patients had both baseline and post-treatment PET scans.. All seven patients improved with treatment and were in remission at the time of the second PET scan. Both SPM and ROI analyses showed that treatment with mood stabilizers had no significant effect on brain 5-HT2A receptor binding in manic patients.. This study suggests that changes in brain 5-HT2A receptors are not involved in the antimanic effects of mood stabilizers however, we cannot exclude the possibility of 5-HT2A receptor involvement in down-stream signaling pathways.

Topics: Acute Disease; Adult; Antimanic Agents; Bipolar Disorder; Brain; Contrast Media; Female; Humans; Lithium; Male; Middle Aged; Positron-Emission Tomography; Pyrimidinones; Receptor, Serotonin, 5-HT2A; Valproic Acid