Possible Interaction Between Lopinavir/Ritonavir And Valproic Acid Exacerbates Bipolar Disorder
Bibliographic record
Abstract
OBJECTIVE: 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. CASE SUMMARY: 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. DISCUSSION: 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. CONCLUSIONS: 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".