Schizophrenia Research Trends

108Stephen I. Deutsch, John Mastropaolo and Barbara L. SchwartzOur group conducted an open-label investigation to evaluate the therapeutic efficacy,safety, and tolerability of adjuvant topiramate in 12 patients with schizophrenia andschizoaffective disorder (Deutsch et al., 2003; see also case report by Drapalski et al., 2001).An optimal dose of topiramate was determined for each of the 12 patients during a slow fourweektitration procedure. Patients were maintained on topiramate and their stableantipsychotic medications for eight weeks, after which topiramate was tapered anddiscontinued. Patients were followed for an additional four weeks on their stableantipsychotic medications. Clinical measures of efficacy (e.g., Positive and NegativeSyndrome Scale), cognitive measures (e.g., recall and recognition, verbal fluency, wordretrieval, Trails A and B), and safety measures (e.g., postural sway, weight) were assessedduring four phases of the study: baseline, four weeks on adjuvant topiramate (week 4), eightweeks on adjuvant topiramate (week 8), and at follow-up (four weeks after topiramate wasdiscontinued). The results showed that topiramate administration (average dose = 110mg/day) significantly decreased scores on the Positive and Negative Syndrome Scale.Specifically, total scores at baseline were significantly higher than total scores at week 4 andweek 8 on topiramate. After topiramate was discontinued at follow-up, total PANSS scoresincreased compared with week 8. Scores on the negative subscale of the PANSS showed asimilar pattern. Negative symptoms were higher at baseline relative to week 4 and marginallyso at week 8 (P = .06). After topiramate was discontinued, negative scores at follow-upshowed a marginally significant increase compared with those at week 8 (P = .052). For thegeneral psychopathology scale, there was a significant difference between baseline and week8 scores, and between week 8 and follow-up scores. Topiramate did not have a significanteffect on scores from the positive symptom subscale of the PANSS, the Quality of Life Scale,or the CGI scale. Adjuvant topiramate did not have global deleterious effects on cognitivefunction. Consistent with previous reports, topiramate decreased the number of wordsproduced in the verbal fluency test; however, this effect was selective and reversible after thedrug was discontinued. There was also a trend for topiramate to decrease working memorymeasured by the Letter-Number Sequencing Test in the WAIS-III (Wechsler, 1997). It isnoteworthy, however, that topiramate did not have a detrimental effect on recall orrecognition performance. In fact, an exploratory look at recognition d’ scores (measure ofrecognition discrimination) showed that patients’ recognition after eight weeks on topiramatewas significantly higher than at baseline. Although topiramate was associated with decreasedword finding, these recognition data point to the possibility that adjuvant topiramate mightalso have salutary effects on cognition in schizophrenia. Because topiramate administrationcan cause dizziness and unsteadiness, we used a measure of postural stability to assess thesafety of topiramate. Data collected with the postural stability test revealed that topiramatedid not increase instability or balance problems in schizophrenia patients.In summary, the data are provocative, supporting continued exploration of NMDAreceptor agonist strategies for the treatment of schizophrenia. As discussed, the therapeuticefficacy of at least some of these interventions may be influenced by state of illness (e.g.,exacerbated versus remitted state) and the specific antipsychotic medication that is coprescribed.Also, there may be discrete domains of psychopathology or specific symptomsthat are sensitive to the therapeutic actions of NMDA receptor agonist interventions.