Forensic psychology: A guide to practice

Metabolic side-effects of atypical antipsychotics have led to concern about their relative safety compared with low doses of conventional neuroleptics. Akathisia is an often misdiagnosed side-effect, which leads to non-compliance and sometimes even exacerbation of psychosis or suicidal behaviour. In fact, little is known about the differences between antipsychotic drugs in clinical practice, since only as few as 20% of patients may be eligible for studies comparing antipsychotic medications with each other. The aim of this study was to find out if the use of conventional antipsychotics is associated with an increased risk of akathisia (compared with atypical antipsychotics) even when low doses of conventional antipsychotics are used. The Barnes Akathisia Rating Scale was used to evaluate akathisia in 100 outpatients on antipsychotic medication. Conventional antipsychotics were associated with an increased risk of akathisia compared with atypical antipsychotics, although the chlorpromazine equivalent doses of conventional antipsychotics were lower than those of the atypicals. An additional akathisia-provoking effect of SSRIs could not be ruled out. The results suggest favouring atypical antipsychotic medication in patients who may easily develop akathisia.     

Clozapine-induced akathisia in children with schizophrenia

Akathisia is a relatively rare side effect with the newer atypical antipsychotic agents, particularly clozapine, and is easily misdiagnosed in children. As children are often unable to describe their symptoms verbally, their akathisia can be misdiagnosed as worsening of their psychosis, prompting an unnecessary increase in their neuroleptic dose. Two cases of childhood-onset schizophrenia associated with clozapine-induced akathisia responsive to beta-blocker treatment are described. Akathisia should be considered in all cases of apparent nonresponse to atypical antipsychotics.     

Treating movement disorders and akathisia as side effects of antipsychotic pharmacotherapy

One of the most common reasons for switching antipsychotic medication is to reduce the burden of side effects, particularly movement disorders and akathisia associated with typical antipsychotics. Adjusting the antipsychotic dose and, if necessary, switching treatment to an antipsychotic with a low extrapyramidal symptom liability may help to optimize the clinical management of schizophrenia. Switching from a typical to an atypical antipsychotic or between atypical antipsychotics involves considering a variety of factors relating to the patient, illness, medication, and the patient's environment.     

Akathisia: clinical phenomenology and relationship to tardive dyskinesia.

Akathisia and tardive dyskinesia (TD) are disorders of movement that are often associated with administration of antipsychotic medication. We surveyed 196 outpatients in a schizophrenia clinic, all receiving antipsychotic medication, for the presence of these disorders. Clinical global ratings of akathisia were reliable. Akathisia was found in 36% of patients, and TD in 23.5%. Akathisia was disproportionately common in patients receiving high-potency neuroleptics. The data affirmed recent revisions in the dose-equivalence formulas used with fluphenazine decanoate. Akathisia and TD did not seem to be interrelated. Because akathisia is common and often limits medication dose and contributes to noncompliance, psychiatrists must take this into account when prescribing antipsychotic medication.     

Treatment of neuroleptic-induced akathisia with the 5-HT2A antagonist trazodone

Akathisia is a common and distressful extrapyramidal adverse side effect usually resulting from the use of antipsychotic medications. Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance. Unfortunately many patients fail to respond to standard management of akathisia. In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia. Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. This open-label pilot study investigates the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least "mild akathisia" on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. These observations suggest the use of trazodone as a beneficial and relatively safe medication for the treatment of antipsychotic medication-induced akathisia. Further study in the context of a double-blind, placebo-controlled trial is mandated to substantiate these preliminary findings.     

Prevalence of movement disorders in adolescent patients with schizophrenia and in relationship to predominantly atypical antipsychotic treatment

Objective To examine prevalence of movement disorders (MDs) such as tardive dyskinesia (TD), parkinsonism or akathisia in an adolescent population with schizophrenia and in relationship to predominantly atypical antipsychotic treatment. Method Ninety-three patients (aged 19.6±2.2 years) were ascertained in this cross-sectional/retrospective study. 76 patients (81.7%) received atypical, 10 (10.8%) typical antipsychotics and 7 (7.5%) combinations of atypical/typical antipsychotics. MD symptoms were assessed using Tardive Dyskinesia Rating Scale (TDRS), Abnormal Involuntary Movement Scale (AIMS), Extrapyramidal Symptom Scale (EPS), Barnes Akathisia Scale (BAS). Results Movement disorder symptoms were found in 37 patients (39.8%) fulfilling strict/subthreshold criteria for TD (5.4/11.8%), parkinsonism (2.2/25.8%) or akathisia (1.1/11.8%), respectively. Patients treated with typical antipsychotics displayed a significantly higher EPS-score (P=0.036) and a tendency towards a higher BAS-score (P=0.061) compared to patients with atypical antipsychotics. Treatment durations with typical/atypical antipsychotics showed trends towards advantages of atypical antipsychotics with regard to parkinsonism/akathisia symptoms (P=0.061; P=0.054), but not with regard to TD symptoms (P=0.003), possibly due to confounding effects. Conclusion Under treatment with atypical antipsychotics MD symptoms are less prevalent and less pronounced than under typical antipsychotics. We speculate that the finding of relatively high prevalence rates of subthreshold MD symptoms may be, at least partially, explained by previous or combined therapy with typical antipsychotics.     

Neither atypical nor conventional antipsychotics increase mortality or hospital admissions among elderly patients with dementia: a two-year prospective study.

BACKGROUND: Antipsychotics are widely used to manage behavioral disorders in patients with dementia. Recently, serious concerns have been raised about the stroke and mortality risk of atypical antipsychotics when administered to patients with dementia. AIM: The aim of this study was to examine the impact of atypical and conventional antipsychotics on mortality and hospital admissions among Finnish elderly institutionalized patients with dementia in a two-year follow up and to compare their prognosis with that of nonusers. PATIENTS AND METHODS: The authors examined 254 very frail patients with dementia, mean age 86 years, from seven Finnish nursing homes and two hospitals in 1999-2000. Medical records provided information on the use of daily antipsychotic medication; central registers confirmed mortality for up to two years. RESULTS: Nearly one-half (48.4%) of the patients used antipsychotic medication: 37.4% received conventional neuroleptics (N = 95) and 11.0% received atypical antipsychotics (N = 28). The mean number of hospital admissions was higher among the nonusers than among the users of conventional or atypical antipsychotics. Of the users of atypical antipsychotics (risperidone, olanzapine), 32.1% died within 2 years. The respective figures for users of conventional neuroleptics were 45.3%, and for the nonusers, 49.6%. In the Cox proportional hazard model, a high number of medications and the use of physical restraint predicted higher mortality at two years. The use of atypical antipsychotics showed lower risk of mortality, if any. The respective test for conventional antipsychotics was nonsignificant. CONCLUSION: Among these frail and very old patients with dementia, neither the use of atypical antipsychotics nor the use of conventional neuroleptics increased mortality or hospital admissions. The use of restraints, however, doubled the risk of mortality.     

Who are patients on conventional antipsychotics?

The advent of atypical antipsychotics presented psychiatrists with an effective way of treating psychosis without the many side effects associated with conventional agents. Given the superiority of atypical antipsychotics, we examined demographic information and treatment histories of patients currently treated with conventional antipsychotics, especially in regard to treatment with atypical agents. Medication histories and demographic information for 276 patients admitted to an urban hospital were obtained by patient/family interviews and review of medical records. Chi-square and logistic regression tests were used to analyze data for possible predictive factors of which patients within the sample were still receiving conventional antipsychotics for treatment. Seventy-eight (28%) patients were currently being treated with conventional antipsychotics. More than half of them had never received a trial of an atypical agent. African-Americans, who are more likely to suffer adverse effects from conventional antipsychotics, and substance abusers were overrepresented in this group. It is unclear to what extent ethnic or cultural bias played a role in determining medication choice. Because conventional antipsychotics are associated with more side effects and greater medication nonadherence, these patients should be evaluated for appropriateness of a trial with an atypical agent even if they are currently stable with a conventional antipsychotic.     

Does smoking reduce akathisia? Testing a narrow version of the self-medication hypothesis

BACKGROUND: The self-medication hypothesis proposes that schizophrenia patients smoke to decrease their schizophrenia symptoms or antipsychotic side effects, but they usually start smoking before their illness and heavy smoking is not consistently associated with fewer symptoms or side effects. A narrow version of the self-medication hypothesis, heavy smoking reduces akathisia, is explored. METHOD: The sample included 250 outpatients with DSM-IV schizophrenia assessed with the Positive and Negative Syndrome Scale (PANSS) and the Barnes Akathisia Scale. Prevalences were 69% (173/250) for smoking, 39% (98/250) for heavy smoking (> or =30 cigarettes/day), 7% (17/250) for akathisia (Barnes Global score>1), 14% (35/250) for a broader akathisia definition (Barnes Global score>0) and 20% for excited symptoms (>1 on the PANSS factor score). RESULTS: Heavy smoking was not associated with akathisia (41% of patients with akathisia were heavy smokers versus 39% of patients without akathisia; chi2=0.3, df=1, p=0.86), even after correcting for confounding factors and/or using a broader akathisia definition. Heavy smoking was associated with excited schizophrenia symptoms (possibly reflecting agitation). Particularly in patients taking lower doses of typical antipsychotics, excited symptoms, with or without akathisia, were strongly associated with heavy smoking and appear to interact with patients' reports of smoking's calming effect as the main reason for smoking. CONCLUSION: The self-medication hypothesis does not explain increased smoking and heavy smoking in schizophrenia. Moreover, heavy smoking may be associated with more disturbed brain homeostatic mechanisms. Prospective studies need to explore whether temporary increases in cigarette smoking may be associated with periods of higher agitation, with or without akathisia.     

Smoking and schizophrenia: is symptom profile related to smoking and which antipsychotic medication is of benefit in reducing cigarette use?

OBJECTIVE: Smoking rate is disproportionately high among patients with schizophrenia, resulting in significant morbidity and mortality. However, cigarette smoking has been reported to have beneficial effects on negative symptoms, extrapyramidal symptoms, cognitive functioning and mood symptoms. Therefore, smoking cessation may worsen disability in schizophrenia. The association between smoking and these key clinical parameters was examined. Additionally, severity of smoking across four different antipsychotic treatment groups was explored. METHOD: One hundred and forty-six patients with schizophrenia were assessed for smoking using expired carbon monoxide and smoking history. They were administered the Positive and Negative Symptom Scale, The Extrapyramidal Symptom Rating Scale, the Barnes Akathisia Rating Scale, Reitans Trail-making Test (A and B) and General Health Questionnaire-28. RESULTS: There was no difference in the chlorpromazine equivalent dose of any of the medications studied. Atypical agents were associated with significantly lower levels of smoking when compared with typical medications. There was no difference in smoking severity between the individual atypical medications examined. Similarly, there were no significant differences between smoking and non-smoking groups with regard to Positive and Negative Symptom Scale, Extrapyramidal Symptom Rating Scale, Trail-making Test and General Health Questionnaire-28. However, there was a significant difference between these groups with the smoking group demonstrating less akathisia. CONCLUSIONS: Smoking is not associated with positive, negative cognitive and mood symptoms in schizophrenia. Smoking is associated with lower levels of antipsychotic induced akathisia. Clinicians should not be discouraged from helping patients stop smoking for fear of worsening symptoms. However, akathisia may emerge upon cessation of smoking. Switching patients from typical to atypical antipsychotics may assist patients with schizophrenia to give up smoking.     

Akathisia--diagnostic dilemma and behavioral treatment

Akathisia, an involuntary movement disorder resulting from exposure to antipsychotics, is characterized by subjective restlessness and a strong desire to move about. The diagnosis is often complicated by the overlapping symptoms of pseudoakathisia, chronic akathisia and tardive dyskinesia. This report deals with a patient with schizophrenia who developed akathisia after exposure to antipsychotics. Later, she developed movements that were more like pseudoakathisia and tardive dyskinesia rather than acute akathisia. On failure of anti-akathisia medication, she was treated with a behavioral regime to which her akathisia responded. This behavioral regime used the technique of distraction as a primary tool. This case report highlights the diagnostic difficulties in akathisia and the application of behavioral treatment for akathisia that is non-responsive to anti-akathisia medication.     

Incidence of tardive dyskinesia with typical versus atypical antipsychotics in very high risk patients.

Our aim was to study the risk of developing tardive dyskinesia in highly vulnerable patients (i.e., middle-aged and older adults with borderline dyskinesia) treated with conventional versus atypical antipsychotics.We examined the cumulative incidence of definitive tardive dyskinesia at 1, 3, and 6 months during antipsychotic treatment among 240 outpatients at least 45 years of age who had borderline tardive dyskinesia at baseline.Patients treated with conventional antipsychotics were approximately two times more likely to develop definitive tardive dyskinesia during the study period compared with those treated with atypical antipsychotics (p <.001). This difference was found despite patients in the atypical antipsychotic group being significantly older and having more severe extrapyramidal symptoms at baseline than those prescribed typical antipsychotics.Among patients at a very high risk for worsening tardive dyskinesia, the use of atypical antipsychotics was associated with a significantly lower risk of developing definitive tardive dyskinesia compared with conventional antipsychotics.     

Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: clinical implications.

OBJECTIVES: This paper gives an overview of studies on the association between dopaminergic neurotransmission and the subjective experience of patients with schizophrenia. METHODS: We undertook a review of the literature. RESULTS: Dopaminergic neurotransmission may be relevant for subjective experience. Higher striatal D2 receptor occupancy by typical and atypical antipsychotics is related to worse subjective experience, more severe negative symptoms, and depression. Individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic-blocking drugs. There is preliminary evidence that a window of striatal D2 receptor occupancy between 60% and 70% is optimal for the subjective experience of patients. These occupancies are often reached even with low dosages of antipsychotic drugs. CONCLUSIONS: Reaching an optimal dopamine D2 receptor occupancy is clinically relevant, since subjective experience associated with antipsychotic medication is related to medication compliance. Antipsychotic drug dosages often need to be lower than levels in common use.     

Serum iron and ferritin in acute neuroleptic akathisia

Acute akathisia is a common and disturbing side effect of classic antipsychotic medication. Some evidence suggests a role for iron deficiency in chronic and tardive akathisia. In acute akathisia, however, the data are contradictory. Serum iron and ferritin levels of 33 inpatients with acute akathisia during classic neuroleptic medication were compared with those of 23 patients on classic neuroleptics without this side effect. Akathisia was rated by means of the Hillside Akathisia Scale. The groups were balanced for age (mean 38.5+/-14.5), medication (butyrophenone- and phenothiazine-derived neuroleptics) and diagnosis (schizophrenia, schizoaffective disorder, psychotic affective disorder). Patients with acute akathisia had significantly lower serum ferritin levels than the patients in the control group. However, the ferritin (56. 94+/-39.54 ng/ml) and iron (88.52+/-40.0 mg/dl) levels in these patients were within the normal range (ferritin 30-300 ng/dl, iron 80-180 mg/dl). No correlations between serum iron or ferritin and akathisia ratings could be found. Although some reduction in serum ferritin was found in patients with acute akathisia compared to patients without akathisia, the difference was small and the ferritin levels were within the range of the normal population. These findings suggest a minor role for iron deficiency in acute akathisia.     

The effects of atypical antipsychotic medications on psychosocial outcomes

This review examines the question--Do atypical antipsychotic medications improve psychosocial outcomes?--by examining studies that compared the effects of atypicals to conventional antipsychotics or to other atypical medications. The authors reviewed randomized clinical trials of atypical antipsychotic medication that included psychosocial variables as outcomes. Findings from 31 published studies on more than 12,000 individuals generally showed that atypical medications led to significant improvements in negative symptoms compared to conventional antipsychotics. Effects on global assessment of psychosocial functioning and on the quality of life were mixed with only about half the studies reporting significant improvements. Olanzapine yielded the best results on psychosocial functioning; remoxipride was found to yield few significant changes on these variables. This review provides evidence that some atypical antipsychotics may have direct effects on some of the psychosocial disabilities that result from serious mental illness.     

Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications

OBJECTIVE: Mortality rates in the year following new antipsychotic medication starts for neuropsychiatric symptoms of dementia were compared with rates after starts of other psychiatric medications. METHOD: The retrospective, cohort study used national data from the Department of Veterans Affairs (fiscal years 2001-2005) on patients older than 65 years who began outpatient treatment with psychiatric medication following a dementia diagnosis (N=10,615). Twelve-month mortality rates were compared in patients taking antipsychotics and those taking other psychiatric medications. The authors controlled for confounding by using multivariate models and propensity-scoring methods. Secondary analyses included a no-medication group and examination of mortality causes. RESULTS: All groups taking antipsychotics had significantly higher mortality rates (22.6%-29.1%) than patients taking nonantipsychotic medications (14.6%). Adjusted mortality risks for atypicals and for combined atypical and conventional antipsychotics were similar to those for conventional antipsychotics. The mortality risk was significantly lower for nonantipsychotic medications than conventional antipsychotics. Except for anticonvulsants, the adjusted risks for all individual classes of nonantipsychotics were significantly lower than the risk for antipsychotics. Mortality risks did not change over 12 months. The proportions of patients taking antipsychotics who died from cerebrovascular, cardiovascular, or infectious causes were not higher than rates for those taking nonantipsychotic psychiatric medications. CONCLUSIONS: Antipsychotic medications taken by patients with dementia were associated with higher mortality rates than were most other medications used for neuropsychiatric symptoms. The association between mortality and antipsychotics is not well understood and may be due to a direct medication effect or the pathophysiology underlying neuropsychiatric symptoms that prompt antipsychotic use.     

Antipsychotic medication and cognitive function in schizophrenia

Antipsychotic polypharmacy and excessive dosing still prevail worldwide in the treatment of schizophrenia, while their possible association with cognitive function has not well been examined. We examined whether the "non-standard" use of antipsychotics (defined as antipsychotic polypharmacy or dosage >1,000 mg/day of chlorpromazine equivalents) is associated with cognitive function. Furthermore, we compared cognitive function between patients taking only atypical antipsychotics and those taking only conventionals. Neurocognitive functions were assessed in 67 patients with chronic schizophrenia and 92 controls using the Wechsler Memory Scale-Revised (WMS-R), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Wisconsin Card Sorting Test (WCST), and the Advanced Trail Making Test (ATMT). Patients showed markedly poorer performance than controls on all these tests. Patients on non-standard antipsychotic medication demonstrated poorer performance than those on standard medication on visual memory, delayed recall, performance IQ, and executive function. Patients taking atypical antipsychotics showed better performance than those taking conventionals on visual memory, delayed recall, and executive function. Clinical characteristics such as duration of medication, number of hospitalizations, and concomitant antiparkinsonian drugs were different between the treatment groups (both dichotomies of standard/non-standard and conventional/atypical). These results provide evidence for an association between antipsychotic medication and cognitive function. This association between antipsychotic medication and cognitive function may be due to differential illness severity (e.g., non-standard treatment for severely ill patients who have severe cognitive impairment). Alternatively, poorer cognitive function may be due in part to polypharmacy or excessive dosing. Further investigations are required to draw any conclusions.     

Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient.