Psychopharmacology (2003) 171:58–67 DOI 10.1007/s00213-002-1160-9 ORIGINAL INVESTIGATION Laura Weiss Roberts · Teddy D. Warner · Khanh P. Nguyen · Cynthia M. A. Geppert · Melinda K. Rogers · Brian B. Roberts Schizophrenia patients and psychiatrists perspectives on ethical aspects of symptom re-emergence during psychopharmacological research participation Received: 8 November 2001 / Accepted: 24 May 2002 / Published online: 17 May 2003  Springer-Verlag 2003 Abstract Rationale: Study designs involving medica- tion-free intervals have become the subject of controversy in the current dialogue on the ethics of serious mental- illness research. Methods: Schizophrenia patients (n=59; response rate 75%; 48% inpatients) and psychiatrists (n=70; response rate 83%) responded to ten questions about a hypothetical scenario in which a schizophrenia study participant experienced the re-emergence of serious symptoms during the “wash-out” phase of a psychophar- macological trial. Patients provided their personal views, and psychiatrists gave their personal views and made predictions as to how schizophrenia patients in general would respond. Results: Schizophrenia patients and psychiatrists judged the hypothetical protocol as moder- ately harmful. Both expressed relatively low likelihood of willingness to participate in the study, given this potential outcome. Schizophrenia patients and psychiatrists found the decision fairly easy. Psychiatrists underestimated the level of harm and overestimated the difficulty of the decision as perceived by schizophrenia patients. Schizo- phrenia patients acknowledged that the offer of money and request by their doctor or family would increase the likelihood of their participation, and psychiatrists accu- rately predicted these responses. In hypothetical decisions about the symptomatic study participant, 38% of patients and 39% of psychiatrists said they would allow him to leave the hospital. A majority of both groups (63% and 52%, respectively) indicated that medication should be given despite the study participant’s objection. Psychia- trists incorrectly predicted this response, expecting in- stead that most schizophrenia patients would support the discharge request and few would support involuntary administration of medication. Patients and psychiatrists offered similar reasons for participation decisions but differed in their strategies for handling the situation. Conclusion: These findings suggest potential strengths of decisionally capable schizophrenia patients in assessing ethically important design elements of psychopharmaco- logical trials. Implications for informed consent for research, expectations of the therapeutic obligations of clinical investigators, and the role of psychiatric advance directives in psychopharmacological research are out- lined. Keywords Wash out · Psychiatry · Research · Schizophrenia · Ethics Introduction Study designs involving medication-free intervals, in- cluding the “wash-out” phase at the beginning of many clinical trials, have become the subject of considerable controversy in the current dialogue about the ethical acceptability of research involving seriously mentally ill participants (Carpenter et al. 1997; American Psychiatric Association 2000). Rationales offered to justify wash-out periods in psychopharmacological trials hinge on scien- tific and methodological issues. A washout design is valuable because it helps to temporally and physiologi- cally isolate the experimental intervention, which, in turn, clarifies the effects of the compound under evaluation (Lieberman et al. 1999; Yuwiler and Wetterberg 2000; World Medical Association General Assembly 2001). However, objections to medication-free intervals are based on the grounds that human researchers have the duty to help, not harm, study participants (Rothman and Michels 1994; Appelbaum 1996). It is argued that L.W. Roberts · T.D. Warner · K. Nguyen · C. Geppert · M. Rogers Empirical Ethics Group, Department of Psychiatry, University of New Mexico Health Sciences Center Institute for Ethics, University of New Mexico School of Medicine, New Mexico, USA B.B. Roberts Chief of Inpatient Psychiatry, Albuquerque Veterans Affairs Medical Center, Albuquerque, New Mexico, USA B.B. Roberts Department of Psychiatry, University of New Mexico School of Medicine, New Mexico, USA