Acute antipsychotic-induced movement disorders (AIMD) are clinically relevant since they are frequently associated with high subjective distress, and since over the long-term they can negatively impact treatment adherence of patients with schizophrenic psychoses. This review article summarizes the relevant studies on the prevalence, risk factors, prevention and treatment options and instruments for early prediction of acute AIMD in schizophrenic psychoses. The current evidence and treatment recommendations are divided into three main areas: acute dystonia, akathisia, and parkinsonism. For the treatment of acute dystonia trihexyphenidyl and biperiden have shown their efficacy. Considering pharmacological treatment of akathisia, there is some preliminary evidence for medication with lipophilic beta-receptor blockers (propranolol and pindolol), clonidine, benzodiazepines, mianserin, mirtazapine und trazodone. The treatment options for drug-induced parkinsonism include reduction or switching from one antipsychotic to another with a lower affinity for dopamine D2 receptors, amantadine or in the regular administration of anticholinergic drugs. In conclusion, acute AIMD is easily to recognize but is not always effectively and durably treated. Early recognition and treatment of acute AIMD could be associated with improved treatment outcomes.

The management of clozapine (CLZ)-induced adverse events affects patient prognoses. Akathisia is a relatively rare adverse event related to CLZ administration and thus the management of this syndrome is not well established. Here, we report a case of treatment-resistant schizophrenia wherein CLZ-induced akathisia was successfully managed with gabapentin enacarbil (GE). The patient was a 39-year-old woman who had been treated with atypical antipsychotics other than CLZ for three years with poor tolerability. Initiation of CLZ (400 mg/day) attenuated her psychotic symptoms, but was followed by moderate akathisia. Neither benzodiazepines nor biperiden improved the akathisia; however, akathisia was finally diminished with co-administration of GE. GE facilitated a dosage increase in CLZ (450 mg/day) for the improved management of pyschotic symptoms, and thus indirectly contributed to treatment of the patient's schizophrenia. We suggest that GE is a useful candidate for the management of CLZ-induced akathisia. The improved management of treatment-induced akathisia and other adverse events can extend the potential application of CLZ for treatment-resistant schizophrenia.

Background: Cognitive impairment in schizophrenia can result in considerable difficulty in performing functions of daily life or social rehabilitation. Cognitive impairment in schizophrenia is related to various factors, such as the psychotic severity, aging, medication, and brain-derived neurotrophic factor (BDNF). To date, however, no studies investigating the impact of these factors on cognitive functioning in chronic schizophrenia patients have been performed. Objective: The aim of this study is to identify those factors that influence the cognitive functioning in patients with chronic schizophrenia. Methods: Sixty-five of 116 long-term hospitalized chronic schizophrenia patients (63.8 ± 12.1 years old, M/F = 29/36) were enrolled this cross-sectional study. We investigated the relationship among the patients' age, psychotic severity, treatment medication, serum BDNF levels, and cognitive functioning (measured by the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia; BACS-J). Additionally, we performed a multivariable linear regression analysis. Results: According to the partial correlation analysis, certain parameters [i.e., age, chlorpromazine (CP) equivalent, biperiden (BP) equivalent, and serum BDNF] were significantly correlated with cognitive functioning, including working memory (WM), motor function (MF), attention and processing speed (AP), and executive function (EF). For the multivariate analysis, the MF component, which had the highest correlation, was selected as the dependent variable, and the independent variables included age, Manchester Scale for chronic psychosis (ManS) total score, CP equivalent, BP equivalent, serum BDNF, estimated full scale IQ, and years of education. According to the multiple regression analysis of this model, R (multiple regression coefficient) was 0.542, the adjusted R2 (coefficient of determination) was 0.201, and only BP equivalent (β = -0.305, p = 0.030), but not age, ManS score, CP equivalent, or serum BDNF, could significantly explain MF at the 5% significant level. Conclusion: In conclusion, aging, medication (administering more antipsychotics or anticholinergics), and serum BDNF concentration are significantly correlated with cognitive dysfunction in chronic schizophrenia patients but not with the severity of psychotic symptoms. Furthermore, only the anticholinergic dosage had a significant causal relationship with MF. Thus, the use of anticholinergics in chronic schizophrenia patients with deteriorating cognitive functioning must be reconsidered.

Data sourcesCochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, EBSCO (Cumulative Index to Nursing and Allied Health Literature, LILACS, BIREME, Virtual Health Library (Latin American and Caribbean Health Science Information database), Zetoc Conference Proceedings, the US National Institutes of Health Ongoing Trials Register, (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.Study selectionThe review included randomised controlled trials, irrespective of their language of publication or publication status. Participants could be outpatients or inpatients. The review included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded.Data extraction and synthesisStandard Cochrane methodological processes were followed.ResultsThirty-nine studies that randomised 3520 participants were included; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those. We found low quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, three studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, five studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, seven studies, 682 participants). We found very low quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per five minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, one study, 27 participants), and incidence of producing greater than 0.1 g of saliva over five minutes (RR 1.45, 95%CI 1.13 to 1.86; P = 0.004, one study, 175 participants).However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low quality evidence of a small benefit for amifostine in terms of quality of life (ten-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, one study, 180 participants), but insufficient evidence at the end of and up to three-month post radiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24-month post radiotherapy.There was low quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, five studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, three studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, four studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, three studies, 524 participants).The authors founded insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival and quality of life. There was some low quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, five studies, 389 participants).The authors found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects. There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse and Venalot Depot (coumarin plus troxerutin).ConclusionsThere is some low quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three-month post radiotherapy). However, it is less clear whether or not this effect is sustained to 12-month post radiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.