Urinary incontinence and enuresis are well-known side effects of clozapine. However, clinical experience has shown that patients also suffer from diverse lower urinary tract symptoms (LUTS). The natural course of clozapine-related LUTS is unclear. Thus, a longitudinal follow-up study is needed. A total of 101 subjects who were taking clozapine initially participated. Their LUTS were evaluated using the International Prostate Symptom Score (IPSS), other questionnaires, and a medical records review. After 2 years, 87 of the original subjects could be contacted, and the status of their LUTS was re-evaluated. The average IPSS total was 7.4 +/- 5.9 at the initial evaluation. Although only 11 subjects (10.9%) reported actual incontinence, 42 subjects (41.6%) were found to have clinically significant LUTS (IPSS total score > or =8). No influencing factors could be found among the demographic and clinical variables. At the follow-up, the average IPSS total (7.9 +/- 6.0) and the percentage of subjects with clinically significant LUTS (43.7%) had both increased, although the change was not statistically significant. The prevalence of LUTS in clozapine-medicated patients was higher than in the general population of the same age. However, the prevalence of incontinence was only a quarter of that of LUTS. If clinicians focus only on incontinence, distress from LUTS will not receive appropriate attention. Furthermore, contrary to literature observations, clozapine-related LUTS did not remit easily but rather persisted even into the long-term maintenance phase. More concern should be directed at these troublesome and often neglected side effects.
This study was conducted to delineate the relationship between self-reported side effects and psychopathology in schizophrenia patients. Patients with schizophrenia completed the Liverpool University Neuroleptic Side Effects Rating Scale for subjective side effects and were evaluated with the Positive and Negative Syndrome Scale for their psychopathology. Based on a series of multiple linear regression analyses, we derived a model accounting for the relationships among the specific domains of psychopathology and red herring (RH) items of the Liverpool University Neuroleptic Side Effects Rating Scale in predicting subjective side effects. The model with anxiety/depressive symptoms and RH serving as mediators between positive symptoms and side effects was found to show good fit. Positive symptoms caused mostly anxiety symptoms and tendency to report RH items, whereby resulting in over-generalized reporting of subjective side effects. However, a large proportion of variance of side effects was explained by RH, which was only partially explained by positive symptoms alone. Therefore, patients with severe levels of positive and anxiety/depressive symptoms may be prone to nocebo-like effects of antipsychotics. Studies that include acute stage patients presenting severe levels of these symptoms should not rely only on the subjective report of side effects but also apply objective measures.
Poor adherence to clozapine treatment represents an important problem in clinical practice because additional useful treatment options are unavailable. Although switching to risperidone long-acting injection (RLAI) has been recommended for those with compliance problems, this medication has been found to be less suitable for patients who previously received clozapine. Based on the suggested beneficial effects of RLAI, such as higher rates of treatment continuation and patient satisfaction, and the possible effectiveness of oral risperidone augmentation, it seems worthwhile to try RLAI augmentation for clozapine non-adherence. In this article, we present the cases of four patients with schizophrenia undergoing combined treatment with RLAI and clozapine for more than one year after multiple relapses related to clozapine non-adherence. Durations and frequencies of hospitalizations markedly declined after RLAI augmentation. Indeed, three patients receiving RLAI and clozapine for 1.2-3.5 years were never hospitalized during this period. The lengths of hospitalizations before and after augmenting with RLAI were 54.7 +/- 33.1 and 4.2 +/- 4.2 days/year, respectively. Participants also showed great improvements in social skills. These findings suggest the possible beneficial effects of RLAI augmentation in cases of clozapine nonadherence. However, controlled clinical trials are necessary to confirm whether RLAI augmentation represents a useful treatment option for patients who have not adhered to clozapine treatment.
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