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Update: D Psych&o-pie Drag I 5

This section will appear in the Journal from time to time as new important reports on drug-psychotropic drug interactions are published. Since the authors are not bound by only scientific studies and random control trials, even technical reports from work in progress in laboratories, case reports, and early observations will be included. We welcome the readership to bring to our attention important interactions that we have overlooked and should be considered for citation in this section. It is our hope to move the scope of reporting to include technical reports, Food Drug Administration (FDA) communications, laboratory reports, and so forth, and not limit citations only to refereed journals. Thus, alerts will be more timely and not delayed by publication schedules.

Tames 1. Strain, M.D.,* Gina Caliendo, Pharm. D, R.Ph.,* and carol himelein, RI% t

In September 1996 General Hospital Psychiatry pub- lished “Drug-Psychotropic Drug Interactions and End Organ Dysfunction: Clinical Management Rec- ommendations, Selected Bibliography, and Updat- ing Strategies” [l]. This special issue included a critical review of 23,000 articles to select the “creme de la creme” for consultation psychiatrists. Eighty- two studies were reported, and along with specific guidelines for drug-psychotropic drug administra- tion and interactions. Eleven periodicals were iden- tified for ongoing review which would allow the psychiatrist to be “updated” on an ongoing basis [Il.

The original list of 82 articles was focused on general information, guidelines for generic groups of drugs, important reviews which bound ideas together, and templates to enable enhanced clinical practice. The current ongoing update is more spe- cific in that it includes technical reports (e.g., psy- chotropic drugs and protease inhibitors); new symptoms with new drugs (e.g., risperidone); with- drawal reactions (e.g., venlafaxine withdrawal re- action) (Letter to the Editor, American Journal of Psychiatry); possible serotonin syndromes associ- ated with tramadol and sertralin coadministration, and so forth. In addition to the citation and a brief summary of these “new finds,” there is also a Com- ment describing the significance of the report. Fi- nally, the selections will also have a focus on re- ports particularly useful for teaching primary care physicians: the “teaching paper.” At times a special

*Mount Sinai School of Medieine. Wharmacia & Upjohn Company.

General Hospital Psychiatry 19,429-431, 1997 0 1997 Elsevier Science Inc. All rights reserved. 655 Avenue of the Americas, New York, NY 10010

topic will be the focus, e.g., cancer chemotherapy and psychotropic drugs.

Mason BJ, Blackborn KH: Foss&b sez~-&Ar~ syn- drome associated with tramad& ~~,~~~~e eo- administration. Ann Pharnrac 31:175-177, 1997 (located in CA/CTF 26(May):33, 1997) This case report describes a patient admitted due to atypical chest pain with sinus tachycardia. The pa- tient had been on multiple medicatiuns including sertraline 100 mg qam for over a year, and tramadol 300 mg daily for 3 weeks. On admission she was complaining of confusion, psychosis, sundowning, diaphoresis, and tremor, all consLtent with seroto- nin syndrome. Symptoms abated 24-36 hours after tramadol was discontinued and sertraline dosage reduced. Combination therapy was restarted un- eventfully with lower doses.

Comment: The potential for this interaction is signif icant because sertraline is widely used already, and tra- madol is gaining use because of its nonaddictive, non- narcotic analgesic activity. The proper management of this interacfion is unclear at this fime because there is lack of data.

Klamerus KJ, Parker VD, Rudct@h RC, et al.: Effects of age and gender on venlafxine and 0-desmethylvenlafaxine pharmaedkinetics. Phar- macother l&915-23, 1996 (located in CAKTF 16{Jan):3, 1997) This pharmacokinetic trial enrolled nine male and nine female nonpsychiatric patients in each of two

429 ISSN 0163~8343/97/$17.00

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J. Strain et al.

age groups. The first group was 21-44 years old and the second was 60-80 years old. Pharmacoki- netics were evaluated after a single oral 50 mg dose and after 3 days of 50 mg three times daily. Phar- macokinetics of venlafaxine and its active metabo- lite 0-desmethylvenlafaxine were similar regard- less of age or gender in both the single and multiple dose trial.

Comment: Though this trial suggests that venlafaxine does not require dosage modifications based on age alone, it is important to note that no pharmacodynamic param- eters were evaluated and these were not patients with depression.

Louis AK, Lannon RA, Kirsch MA, Lewis TB: Venlafaxine withdrawal reaction. Am J Psychiatry (letter) 153:1652,1996 (located in Clin-Alert Jan 32~13, 1997) The authors describe three cases of nausea, dizzi- ness, and diarrhea after withdrawal of venlafaxine. Symptoms began 1-3 days after the dose was de- creased or the drug was withdrawn, and subsided upon reinitiation of venlafaxine.

Comment: Although this was a brief case series, we highlight the information to draw attention to clinically relevant information about a new antidepressant. Clini- cians should be cautious when discontinuing venlafaxine in any patient.

Schnierow BJ, Graeber DA. Manic symptoms as- sociated with initiation of risperidone. Am J Psy- chiatry 153~1235-6, 1996 (located in Clin-Alert Jan 31~26, 2997) The authors describe three cases of mania tempo- rally related to the initiation of risperidone. In all cases, the symptoms responded to dose decreases or discontinuation. In one case, the symptoms re- turned when the drug was restarted, and dissipated with dosage reduction. The authors briefly re- viewed other cases of mania associated with ris- peridone.

Comment: This report highlights a significant event associated with a relatively new antipsychotic agent, and describes clinical management.

Chen B, Cardasis W: Delirium induced by lithium and risperidone combination. Am J Psychiatry 153:1233-1234, 153 (letter) (located in Clin-Alert Jan 32:22, 1997)

A case of delirium temporally related to the initia- tion of risperidone is described. A 69-year-old pa- tient was well maintained on lithium for over 10 years. She was started on amantadine and then risperidone a few weeks later. Over a 3-week pe- riod following the addition of risperidone she de- veloped progressive delirium, requiring hospital- ization. She recovered slowly after all medications were withdrawn. Lithium was later reintroduced uneventfully.

Comment: This case highlights a potential drug inter- action that resulted in hospitalization and significant patient discomfort.

Meyer MC, Baldessarini RJ, Goff DC, Centorrino F: Clinically significant interactions of psycho- tropic agents with antipsychotic drugs. Drug Safety 15:333-346,1996 The authors underscore the clinically significant inter- actions that occur through competition with or induc- tion of hepatic microsomal cytochrome p450 (CYP), especially the CYPlA2 and the CYP2D6 isozymes by which most antipsychotics are oxidized. This situa- tion may lead to elevated concentrations of antipsy- chotics to potentially toxic range and induce adverse responses. The authors elaborate on various potential risks in using combined chemotherapies.

Comment: This is an important review of pharmaco- kinetics and interaction possibilities when psychotropic agents are combined with typical and atypical antipsy- chotic medications.

Elliott RL, Schillcutt SD: Using newer antidepres- sants in the medically ill: an update. Primary Psy- chiatry (May 1996 42-56) Comment: This is an important teaching paper for prima y care physicians which may be helpful to psychiatrists work- ing in the prima y care setting. It demonstrates an effective translation of psychiatric pharmacology into paradigms more suitable for prima y care trainees.

Nemeroff CB, DeVane CL, Pollock BG: Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 153:311-320,1996 This paper describes evidence for distinct profiles of cytochrome I’450 inhibition and drug interaction possibilities by individual antidepressants. It also suggests the need to study the utility of phenotyp- ing in clinical practice since different phenotypes

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may respond differently to different antidepressant References medication.

Comment: This paper highlights the potential individ- ual variability that can OCCUY with the use of antidepres- sants, and the need to have enhanced criteria, e.g., phe- notyping, to improve their clinical application.

1. Strain JJ, Caliendo G, Himelein C, Hammer JS: Drug- Psychotropic Drug Interactions and End Organ Dys- function. In Strain JJ (ed), Consultation-Liaison Psychi- atry Database (1996 Update). Gen Hosp Psychiatry l&300-313, 1996

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