ABSTRACT
BACKGROUND: Pharmacologic treatment of emotional disorders in HIV-infected patients can be more easily optimized by understanding of potential interactions of psychotropic drugs with medications used to treat HIV infection and its sequelae. METHODS: Biotransformation of the antidepressant trazodone to its principal metabolite, meta-chlorophenylpiperazine (mCPP), was studied in vitro using human liver microsomes and heterologously expressed individual human cytochromes. Interactions of trazodone with the azole antifungal agent, ketoconazole, and with human immunodeficiency virus protease inhibitors (HIVPIs) were studied in the same system. RESULTS: Formation of mCPP from trazodone in liver microsomes had a mean (+/- SE) K(m) value of 163 (+/- 21) micromol/L. Ketoconazole, a relatively specific CYP3A inhibitor, impaired mCPP formation consistent with a competitive mechanism, having an inhibition constant (K(i)) of 0.12 (+/- 0.01) micromol/L. Among heterologously expressed human cytochromes, only CYP3A4 mediated formation of mCPP from trazodone; the K(m) was 180 micromol/L, consistent with the value in microsomes. The HIVPI ritonavir was a potent inhibitor of mCPP formation in liver microsomes (K(i) = 0.14 +/- 0.04 micromol/L). The HIVPI indinavir was also a strong inhibitor, whereas saquinavir and nelfinavir were weaker inhibitors. CONCLUSIONS: CYP3A-mediated clearance of trazodone is inhibited by ketoconazole, ritonavir and indinavir, and indicates the likelihood of pharmacokinetic interactions in vivo.
Subject(s)
Antifungal Agents/metabolism , Aryl Hydrocarbon Hydroxylases , Cytochrome P-450 Enzyme Inhibitors , HIV Protease Inhibitors/metabolism , Ketoconazole/metabolism , Oxidoreductases, N-Demethylating/antagonists & inhibitors , Selective Serotonin Reuptake Inhibitors/metabolism , Trazodone/metabolism , Antidepressive Agents, Second-Generation/metabolism , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme System/metabolism , Drug Interactions , Humans , In Vitro Techniques , Indinavir/metabolism , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Nelfinavir/metabolism , Oxidoreductases, N-Demethylating/metabolism , Piperazines/metabolism , Ritonavir/metabolism , Saquinavir/metabolism , Serotonin Receptor Agonists/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Trazodone/pharmacokineticsABSTRACT
BACKGROUND: Some candidates for clozapine treatment may be unable to be given the drug. They may be so severely ill that they cannot or will not ingest a pill; their psychosis may have so compromised their physical status that use of clozapine, which produces a broad range of side effects, would be unsafe; and/or they may require a very rapid control of their behavior. METHOD: Two case reports are described of patients who, although candidates for clozapine, were unable to take or be given the drug. Initial treatment with electroconvulsive therapy (ECT) was tried in both patients prior to use of clozapine. RESULTS: In the two cases described, treatment with ECT prior to clozapine stabilized the patients enough that clozapine could be administered. In both cases, the clozapine appeared to perpetuate the initial clinical response produced by the ECT. CONCLUSION: These case reports suggest that a two-step strategy of ECT followed by clozapine treatment may both facilitate the use of clozapine in some patients and perpetuate the clinical stability produced by ECT alone.
Subject(s)
Clozapine/therapeutic use , Electroconvulsive Therapy , Psychotic Disorders/therapy , Adult , Combined Modality Therapy , Female , Humans , Middle Aged , Psychotic Disorders/drug therapy , Psychotic Disorders/psychology , Treatment OutcomeABSTRACT
This study compared the validity of two promising measures of shame and guilt proneness: revisions of the Harder Personal Feelings Questionnaire (PFQ2; Harder & Lewis, 1987) and the Hoblitzelle Adapted Shame and Guilt Scale (ASGS; Hoblitzelle, 1982). Internal consistency, test-retest stability, factor structure, and construct validity with convergent and discriminant personality dimensions were examined for both scales. In addition to the shame and guilt measures, 63 (37 male, 26 female) mostly freshman college students completed a randomly ordered battery of personality scales theoretically relevant to shame and guilt proneness. Results support the reliability and shame/guilt factor structure of each scale. ASGS Shame correlations appeared marginally more valid with 11 external construct variables than PFQ2 Shame, whereas PFQ2 Guilt was clearly more valid than its corresponding ASGS subscale. New, potentially improved scales were constructed from the factor analyses and from item analyses. However, the resulting scales did not show improved validity.