Traditional Antipsychotic Medications Research Articles

Multimodal prediction of the need of clozapine in treatment resistant schizophrenia; a pilot study in first-episode psychosis

As many as one third of the patients diagnosed with schizophrenia do not respond to first-line antipsychotic medication. This group may benefit from the atypical antipsychotic medication clozapine, but initiation of treatment is often delayed, which may worsen prognosis. Predicting which patients do not respond to traditional antipsychotic medication at the onset of symptoms would provide fast-tracked treatment for this group of patients. We collected data from patient records of 38 first-episode psychosis patients, of whom seven did not respond to traditional antipsychotic medications. We used clinical data including medical records, voxel-based morphometry MRI data and inter-subject correlation fMRI data, obtained during movie viewing, to predict future treatment resistance. Using a neural network model, we correctly predicted future treatment resistance in six of the seven treatment resistance patients and 25 of 31 patients who did not require clozapine treatment. Prediction improved significantly when using imaging data in tandem with clinical data. The accuracy of the neural network model was significantly higher than the accuracy of a support vector machine algorithm. These results support the notion that treatment resistant schizophrenia could represent a separate entity of psychotic disorders, characterized by morphological and functional changes in the brain which could represent biomarkers detectable at early onset of symptoms.

Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review.

Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well-being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. Fifty-eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

Single Quantum Dot Tracking Unravels Agonist Effects on the Dopamine Receptor Dynamics.

D2 dopamine receptors (DRD2s) belong to a family of G protein-coupled receptors that modulate synaptic dopaminergic tone via regulation of dopamine synthesis, storage, and synaptic release. DRD2s are the primary target for traditional antipsychotic medications; dysfunctional DRD2 signaling has been linked to major depressive disorder, attention-deficit hyperactivity disorder, addiction, Parkinson's, and schizophrenia. DRD2 lateral diffusion appears to be an important post-translational regulatory mechanism; however, the dynamic response of DRD2s to ligand-induced activation is poorly understood. Dynamic imaging of the long isoform of DRD2 (D2L) fused to an N-terminal antihemagglutinin (HA) epitope and transiently expressed in HEK-293 cells was achieved through a combination of a high-affinity biotinylated anti-HA antigen-binding fragment (Fab) and streptavidin-conjugated quantum dots (QD). Significant reduction (∼40%) in the rate of lateral diffusion of QD-tagged D2L proteins was observed under agonist (quinpirole; QN)-stimulated conditions compared to basal conditions. QN-induced diffusional slowing was accompanied by an increase in frequency, lifetime, and confinement of temporary arrest of lateral diffusion (TALL), an intrinsic property of single receptor lateral motion. The role of the actin cytoskeleton in QN-induced diffusional slowing of D2L was also explored. The observed dynamic changes appear to be a sensitive indicator of the receptor activity status and might also spatially and temporally shape the receptor-mediated downstream signaling. This dynamic information could potentially be useful in informing drug discovery efforts based on single-molecule pharmacology.

Autophagy and Schizophrenia: A Closer Look at How Dysregulation of Neuronal Cell Homeostasis Influences the Pathogenesis of Schizophrenia.

Autophagy, the process of degrading intracellular components in lysosomes, plays an important role in the central nervous system by contributing to neuronal homeostasis. Autophagic failure has been linked to neurologic dysfunction and a variety of neurodegenerative diseases. Recent investigation has revealed a novel role for autophagy in the context of mental illness, namely in schizophrenia. This article summarizes the phenomenology, genetics, and structural/histopathological brain abnormalities associated with schizophrenia. We review studies that demonstrate for the first time a connection between autophagy malfunction and schizophrenia. Transcriptional profiling in schizophrenia patients uncovered a dysregulation of autophagy-related genes spatially confined to a specific area of the cortex, Brodmann Area 22, which has been previously implicated in the positive symptoms of schizophrenia. We also discuss the role of autophagy activators in schizophrenia and whether they may be useful adjuvants to the traditional antipsychotic medications currently used as the standard of care. In summary, the field has progressed beyond the basic concept that autophagy impairment predisposes to neurodegeneration, to a mechanistic understanding that loss of autophagy can disrupt neuronal cell biology and predispose to mood disorders, psychotic symptoms, and behavioral change.

Advances in the understanding and challenges facing the management of first-episode schizophrenia

Symptoms of schizophrenia typically first appear in adolescence, a time of transition involving biological, social and emotional changes. Schizophrenia and related psychotic illnesses can significantly impair educational and social development; consequently, early identification and treatment is paramount and can affect long-term outcome. Singh (2010) states that early intervention is cost effective and does ameliorate the course of early psychosis, referring specifically to specialist early intervention teams, and their impact on longterm disease outcome and prognosis. Much research is now available in this area, and the papers selected for this supplement focus on intervention at this critical stage, related side effects as well as mortality risk factors associated with schizophrenia. The stress–vulnerability model for schizophrenia suggests that the onset and course of schizophrenia may be determined by an underlying vulnerability, with clinical manifestation being modulated by environmental stressors. It has long been recognized, since the days of Kraepelin (1913), that people with schizophrenia are more likely to be obese and to suffer from metabolic problems such as diabetes mellitus. Leonard et al. review evidence concerning a disordered immune system in schizophrenia and postulate that the relationship between the therapeutic benefits of antipsychotics, the pathology of schizophrenia and these metabolic syndromes are linked to chronic, low-grade inflammation. As maternal infections have been implicated as a causative factor, the resulting inflammatory changes could contribute to neurodevelopmental difficulties, and a sensitized immune system that activates in adolescence. Leonard et al. also discuss the important role played by pro-inflammatory cytokines which modulate neuronal action, differentiation and survival during neurodevelopment, and more specifically influence activity and survival of neurons that utilize neurotransmitters such as serotonin, glutamate and dopamine. Interleukin-6 is particularly important in schizophrenia as it could augment dopaminergic function which, in turn, would affect psychotic symptoms. In addition to the dopaminergic system, some pro-inflammatory cytokines enhance the activity of the glutamatergic system, via the tryptophan–kynurenine pathway, and this might contribute to the cognitive decline sometimes seen in schizophrenia. The inflammation hypothesis of schizophrenia raises the possibility of using anti-inflammatory drugs, such as COX-2 inhibitors, as adjuncts to traditional antipsychotic medication. Van Haren et al. find further evidence to suggest that schizophrenia is a progressive brain disease, and that the most significant decline in grey matter volume occurs in the critical first year of illness. Indeed, there appears to be a linear correlation of grey matter loss with age in schizophrenia, as opposed to the exponential decline seen in healthy individuals. Van Haren et al. also suggest there is a link between the extent of volume loss and severity of symptoms and social functioning, but do acknowledge other studies refute this theory. Although antipsychotic medication remains a confounding factor for grey matter loss, studies in first-degree relatives and at-risk individuals show that cumulative antipsychotic intake can only explain some of these brain volume changes. This review highlights the need for further large studies that follow patients over a long period of time, to further clarify the relationship between brain volume change, antipsychotic intake and outcome. Indeed, the potential to attenuate brain volume changes could potentially improve long-term outcome, which again highlights the need for early intervention and effective treatment in this morbid disease. The advent of ‘atypical’, or second generation antipsychotics, engendered a therapeutic optimism in the treatment of first-episode patients (NICE, 2002). Taylor et al. reviewed the effectiveness of antipsychotic medications in first episode schizophrenia and found traditional randomized controlled trials (RCTs), whilst being necessary, lacked generalizability to real-world clinical scenarios. A need for long-term observational studies to complement the RCTs was recognized, and several high-profile studies have now been published, often using discontinuation rate of antipsychotic medication as the primary outcome. The rationale behind this is that a

Insomnia and excessive daytime sleepiness in psychotic patients taking traditional or atypical antipsychotic medications

The aim of the study was to evaluate quantitative sleep disorders in forty patients with a psychotic disorder (F 20 or F25 at ICD X International Classification), who are taking antipsychotic medication.We studied 100 patients, affected by schizophrenic or schizoaffective disorder, aged from 20 to 65 years old. These patients were divided in four groups each containing 25 people who were taking neuroleptics or atypical antipsychotic (olanzapine, risperidone or aripiprazole).The variability of quantitative sleep disorder was measured using questions 4-5-6 of Hamilton Depression Scale to evaluate early, intermediate or late insomnia, and the Epworth Sleepiness Scale to assess EDS (excessive daytime sleepiness)We all know the sedative effects of neuroleptics, furtherless it is not unexpected that most of the atypical antipsychotics are sedating, and thus have the potential to impair judgement, thinking or motor skills giving the patients the sensation of being different from the other people. Many times we forget that the other side of insomnia is the excessive daytime sleepiness….In the future, we have to manage these disorders, if we want to avoid lack of compliance and further drop out of therapy.

Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity

Currently available antipsychotic medications work primarily by antagonizing D 2 dopamine receptors, thus raising intracellular cAMP levels. We hypothesized that intracellular stimulation of cAMP levels in the CNS would have similar effects to treatment with antipsychotic medication. To test this hypothesis, we studied the effect of an acute treatment of rolipram, an inhibitor of type 4 phosphodiesterases that degrade cAMP, on acoustic startle and prepulse inhibition (PPI) of the acoustic startle response in C57BL/6J mice known to exhibit poor PPI. PPI is disrupted in schizophrenia patients, and the ability of a drug to increase PPI in mice is predictive of antipsychotic efficacy. We show here that acute treatment with rolipram significantly increases PPI at doses that do not alter the acoustic startle response (lowest effective dose 0.66 mg/kg). In addition, rolipram (0.66 mg/kg) blocks the disruptive effects of amphetamine (10 mg/kg) on PPI. At a slightly higher dose (1.0 mg/kg), rolipram also induces catalepsy. Thus, phosphodiesterase-4 (PDE 4) inhibition has many of the same behavioral effects as traditional antipsychotic medications. In contrast to traditional antipsychotics, these effects are achieved through alteration of an intracellular second messenger system rather than antagonism of neurotransmitter receptors. Given previous reports showing rolipram improves cognition, we conclude that PDE 4 represents an important novel target for further antipsychotic drug development.

An Exploration of Central Nervous System Medication Use and Outcomes in Stroke Rehabilitation

Conroy B, Zorowitz R, Horn SD, Ryser DK, Teraoka J, Smout RJ. An exploration of central nervous system medication use and outcomes in stroke rehabilitation. Objective To study associations between neurobehavioral impairments, use of neurotropic medications, and outcomes for inpatient stroke rehabilitation, controlling for a variety of confounding variables. Design Observational cohort study of poststroke rehabilitation. Setting Six inpatient rehabilitation hospitals in the United States. Participants Patients with moderate or severe strokes (N=919). Interventions Not applicable. Main Outcome Measures Discharge disposition, FIM score change, and rehabilitation length of stay (LOS). Results Neurobehavioral impairments and use of many medications, including first-generation selective serotonin reuptake inhibitors, older traditional antipsychotic medications, and anti-Parkinsonian neurostimulants, have a statistical association with poorer outcomes, whereas use of the atypical antipsychotic medications has a positive association with improvement in motor FIM scores. Counterintuitively, use of opioid analgesics is associated with a larger motor FIM score change but not an increase in LOS or reduced percentage of discharge to community. There was significant variation in use of neurotropic medications among the 6 study sites during inpatient stroke rehabilitation. Conclusions There are many opportunities to enhance a stroke survivor’s ability to benefit from acute inpatient stroke rehabilitation through improved understanding of associations of neurotropic medications with outcomes for different patient groups.

Zotepine Versus Placebo in the Treatment of Schizophrenic Patients with Stable Primary Negative Symptoms: A Randomized Double-Blind Multicenter Trial

In contrast to traditional antipsychotic medication, newer, the so called atypical antipsychotic drugs promise to reduce primary negative symptoms in both, acute and chronic schizophrenia and improve quality of life. Zotepine, a D (2)5HT (2A) antagonist, was compared to placebo in this clinical trial to address these issues. In an adaptive, 8-week multicenter, double-blind, randomized, parallel group study, efficacy and tolerability as well as influence on quality of life of zotepine and placebo were compared in 80 schizophrenic patients (53 % males, age 41 +/- 11 years) who experienced stable primary negative symptoms. Efficacy was assessed using the PANSS (primary outcome criterion: PANSS negative score), CGI, and MADRS; safety was controlled by EPS (Simpson-Angus Scale), TDRS and adverse events. Quality of life was evaluated with the SF-36 health questionnaire. After eight weeks of treatment with an average dose of 131 +/- 49 mg/day of zotepine, no superior efficacy of zotepine compared to placebo with respect to the PANSS subscale "negative symptoms could be demonstrated. Although patients receiving zotepine showed a pronounced reduction (per protocol set: -7.8 +/- 5.8) during treatment, it was not statistically different from a marked placebo response (-6.5 +/- 5.8). Similar small but not significant differences between zotepine and placebo were found in other subscales of the PANSS, the CGI and the MADRS. With regards to the quality of life assessment, patients under zotepine showed better results in the physical component scale and psychological well-being scale. In general, zotepine was well tolerated and there was no excess of extrapyramidal symptoms compared to placebo. Zotepine was not superior to placebo in reducing the severity of stable primary negative symptoms in schizophrenic patients in this trial. The main reasons for this finding were a high placebo response in a selected population, a probably too low dose of zotepine, and a short study period. However, several findings show clinical benefit of zotepine therapy in efficacy and quality of life.

Pro-Motion: A Positive Way Forward for Clients with Severe and Enduring Mental Health Problems Living in the Community, Part 2

This is the second part of a two-part article describing a clinical therapeutic intervention, planned and organised by a senior occupational therapist and mental health nursing staff for clients with severe and enduring mental health problems living in the community. The six participants had a diagnosis of schizophrenia or schizoaffective disorder or bipolar illness. Four were receiving the atypical antipsychotic medication, Clozapine. One was receiving Olanzapine, also atypical, and the last was receiving traditional antipsychotic medication, a phenothiazine. These clients were all receiving long-term support from the mental health rehabilitation unit. Participation was voluntary and each client gave written consent to participate and for the findings to be published later. Part 1 described the aims and objectives of the initial group, the selection criteria, and the content and process of the group over a period of 6 weeks. Part 2 describes a subsequent group held with the same clients for another 6 weeks. The outcome measures used in part 1 were the Beck Anxiety Inventory (BAI) (Beck and Steer 1993) and the State-Trait Anxiety Inventory (STAI) (Speilberger 1983) together with verbal and written evaluation. In the second group, it was decided not to repeat the use of the BAI and STAI; instead, a more detailed qualitative questionnaire was issued. The reasons for this are explained. Part 2 goes on to describe the progress of the subsequent group and gives a brief overview of what has happened in further groups since. Client evaluations are illustrated by two case vignettes. The benefits to the other clients are highlighted, together with the possible drawbacks. There is discussion about the possible potential for such groups in the future.

Pro-Motion: A Positive Way Forward for Clients with Severe and Enduring Mental Health Problems Living in the Community, Part 1

This is the first part of a two-part article describing a clinical therapeutic intervention planned and organised by a senior occupational therapist and mental health nursing staff for clients with diagnoses of severe and enduring mental health problems. The six participants had a diagnosis of schizophrenia or schizoaffective disorder or bipolar illness. Four were receiving the atypical antipsychotic medication, Clozapine. One was receiving Olanzapine, also atypical, and the last was receiving traditional antipsychotic medication. These clients were all receiving long-term support from the mental health rehabilitation unit. Participation was voluntary and each client gave written consent to participation and publication later. The aims and objectives of the initial group, the selection criteria and the content and process of the group over a period of 6 weeks are described. The subsequent group, also held for 6 weeks, will be described in part 2, together with a brief overview of the further groups that have taken place since. The evaluation methods of the first group were the Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI) together with verbal and written evaluation. The BAI and the STAI were not repeated in the second group and the rationale for this is explained. The perceived benefits to clients are illustrated with two brief case vignettes. The benefits to other clients are also mentioned, together with the perceived drawbacks. The article concludes with the plans for the second group.

Economic evaluations of novel antipsychotic medications: a literature review

Objective: To evaluate the evidence that novel antipsychotic medications offer a cost advantage compared to traditional antipsychotic medications. Methods: Literature for this review was identified through a computerized search of Medline, Healthstar and Psyc-INFO databases inclusive from January 1989 to January 2002. Articles included in the review were required to include cost evaluation and to be published in peer-reviewed journals. Results: Twenty-two studies met inclusion criteria. All five studies that used experimental designs found that second-generation antipsychotic medications were associated with a cost advantage or were cost-neutral, and, in some cases, improved quality of life. Of the ten studies using a pre-post design, four found an increase in total costs, six reported a decrease in total costs, and four reported increased effectiveness with use of a second-generation antipsychotic. All seven of the simulation studies reported a cost advantage for novel antipsychotics for specific patient populations under certain conditions. Conclusions: The majority of studies found that novel antipsychotics are at least cost-neutral and may offer cost advantages compared to traditional agents. Some studies also reported greater improvement in effectiveness and quality of life when novel antipsychotics were compared to traditional antipsychotic medications. However, it is difficult to draw firm conclusions given the small sample sizes and limited study designs available in this literature.

Access to new medications to treat schizophrenia.

Between 1989 and 1997, the Food and Drug Administration approved four new-generation antipsychotic medications for use in the treatment of schizophrenia. This article examines factors associated with the use of new antipsychotic medications as compared with traditional antipsychotic medications from patient interviews, medical records, and a physician survey administered at schizophrenia treatment sites around the country as part of the Schizophrenia Care and Assessment Program. The following variables were significantly associated with a higher probability of receiving an atypical antipsychotic medication in multiple regression analysis at p < .05: female, younger age, younger age of onset, non-African American, having a higher Positive and Negative Syndrome Scale-Negative Syndrome subscale score. Some physician characteristics were statistically significant in the bivariate results but not in the multivariate analyses. Access to new atypical antipsychotic medications is dependent on more than clinical characteristics. In particular, barriers to access may exist for African Americans. Physician access to information about advances in drug therapies also may play a substantial role in the rate of diffusion of new medications.

Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy.

Little is known about antipsychotic combination therapy, although this practice is becoming increasingly common in the treatment of schizophrenia. Medicaid pharmaceutical claims for a cohort of 836 New Hampshire beneficiaries with schizophrenia or schizoaffective disorder were followed from 1995 through 1999. Use of traditional and atypical antipsychotic medications, antidepressants, anxiolytic hypnotics, and mood stabilizers was tracked monthly. The number of medications, frequency of coprescription, and Medicaid pharmaceutical costs are described. The proportion of individuals with schizophrenia and schizoaffective disorder treated with atypical antipsychotics grew from 43 percent in 1995 to 70 percent in 1999. At the same time, concurrent use of two or more antipsychotic medications quadrupled, increasing from 5.7 percent to 24.3 percent. Persons with schizophrenia were also prescribed more antidepressants (increased from 18.5% in 1995 to 35.6% in 1999), anxiolytics (increased from 19.9% to 33.5%), and mood stabilizers (increased from 17.7% to 30.0%). The increase in multiple agent therapy appears to be broad-based. Data are needed on the effectiveness and cost-effectiveness of these practices to inform clinical decision making and health policy.

Assessment of Schizophrenia in Persons with Severe and Profound Mental Retardation Using the Diagnostic Assessment for the Severely Handicapped-II (DASH-II)

The identification and diagnosis of schizophrenia in persons with severe and profound mental retardation has been a controversial issue. Although it has been established that schizophrenia occurs in this clinical population, persons with odd behaviors characteristic of mental retardation or severe behavior disturbances are often diagnosed with schizophrenia and treated with traditional or atypical antipsychotic medications. The present study assessed schizophrenia in a sample of persons with severe and profound mental retardation using the Diagnositic Assessment for the Severly Handicapped-II (DASH-II), a rating scale which contains purely behavioral criteria that are essential features of various DSM-IV disorders. Three groups of participants were compared; (a) those with an independent psychiatric diagnosis of schizophrenia and a significant elevation on the schizophrenia subscale of the DASH-II; (b) those with a significant elevation on this subscale, but no formal diagnosis of schizophrenia; and (c) controls without any elevation of the DASH-II subscales. Results indicated that the three groups were empirically distinguished across the frequency, duration, and severity dimensions of the DASH-II schizophrenia subscale. Item analyses demonstrated that individuals with a diagnosis of schizophrenia and an elevation of the subscale had higher scores on items containing verbal symptoms of the disorder. Implications of these findings are discussed with respect to the diagnosis of schizophrenia in persons with severe and profound mental retardation, with particular emphasis on the efficacy of the DASH-II for assessing the disorder.

Interventions for Weight Gain in Adults Treated With Novel Antipsychotics.

BACKGROUND: Weight gain is a significant side effect associated with typical and atypical antipsychotic agents. It has the potential to add to the increased morbidity and mortality associated with schizophrenia and schizoaffective disorder. Because the newer antipsychotic medications have proved to be superior to traditional agents in controlling the positive and negative symptoms of schizophrenia, it is additionally critical to address the relationship of these newer agents to weight gain. METHOD: Prior to the availability of novel antipsychotic medication, we looked at a group of 17 residents, of whom 71% had significant weight gain on treatment with traditional antipsychotic medications between 1991 and 1994. This prompted our interest in weight gain, especially after the introduction of novel antipsychotic medications, and our decision to look closely at their diets and help them make changes that would minimize their weight gain. We monitored the effect of a comprehensive primary intervention strategy on controlling obesity in a retrospective study of 32 patients with DSM-IV schizophrenia or schizoaffective disorders. All patients were residents in an adult care facility for formerly homeless persons with serious mental illness. Intervention consisted of complete medical and psychiatric care; switch to a patient-optimal atypical drug; low-calorie, monitored diet; nutritional education; and supportive care. RESULTS: There was no significant change in mean body weight at 12 and 18 months after initiation of intervention. Weight gain was observed in only 30% of study patients after the intervention as opposed to 71% at the start of the study. In general, as the negative symptoms of schizophrenia improved, patients were found to become more receptive to education and to become proactive in their health care. The lack of weight gain was consistently seen with all 3 agents tested-clozapine, olanzapine, and risperidone. CONCLUSION: A patient's diet appears to be a better predictor of weight gain than the choice of novel antipsychotic medication. Clinicians might prescribe nutritional and lifestyle changes alongside medication with weight gain potential.

Acute psychopharmacological management of the aggressive psychotic patient.

Management of the acutely aggressive psychotic patient is a common task in the psychiatric emergency service. Findings from the Epidemologic Catchment Area study, which investigated the prevalence of mental illness in the United States, suggested that patients with serious mental illnesses such as schizophrenia or bipolar affective disorder are two to 15 times more likely to report violent behavior than people with no mental illness (1). This column briefly reviews the neurobiology of aggression and recent findings about the effects of medication noncompliance among patients with severe mental illness. It discusses the advantages and disadvantages of two effective pharmacological interventions for the acute treatment of the aggressive psychotic patient. Neurobiology of aggression The neurobiology of impulsive aggression is the subject of an evolving science that is working toward identifying the medication or combination of medications that will most benefit the violent psychiatric patient (2). Studies using both animal and human models of violent behavior suggest that impulsive aggression involves a complex interaction of neurotransmitter and hormonal activity, societal factors, and individual personality (3,4). Among neurotransmitters, serotonin plays a major inhibitory role in aggressive behavior. Low cerebrospinal fluid levels of 5-hydroxyindolacetic acid (5-HIAA), a major metabolite of serotonin, are significantly correlated with hyperresponsiveness to aversive stimuli and impulsive aggression but not premeditated violence (3). Dopamine and norepinephrine abnormalities may play a role in a patient’s vulnerability to aggressive episodes. Animal studies indicate that increasing brain dopamine and norepinephrine activity significantly enhances the likelihood that the animal will respond to the environment in an impulsively violent manner (3). Atypical antipsychotic medications, which affect both serotonin and dopamine activity, may have primary antihostility properties that the traditional antipsychotic medications lack (5). Several studies have supported the effectiveness of the atypical antipsychotics in the intermediate to long-term management of the violent and psychotic patient (5). In a double-blind study, clozapine and risperidone, both atypical antipsychotics, were found to have a significantly greater primary antihostility effect than haloperidol and placebo (6).

Psychosis and medication: strategies for improving adherence.

The development of traditional anti-psychotic medication has led to improvements in the care of mentally ill people. These medications have been the mainstay of drug treatment for schizophrenia for many years. In recent years, however, the advent of so-called 'atypical' anti-psychotics has enabled patients to be treated without experiencing the range of severe side-effects associated with traditional medicines. Ensuring mentally ill patients take prescribed treatment is seen as an important element of the work of mental health nurses. Adopting approaches which are non-adversarial may provide better outcomes than straightforward advice giving. A combination of psycho-education and a technique known as brief motivational interviewing could provide a useful starting point for nurses. Whether such approaches will be supported given recent declarations on policy intentions remains to be seen.

Assessment and management of antipsychotic-induced adverse events.

To review and discuss the spectrum of adverse events caused by antipsychotic agents that can directly influence the outcome of treatment by interfering with patient acceptance of and adherence to therapy. The adverse effects of traditional and second-generation antipsychotic medications were discussed during a series of clinical workshops attended by psychiatrists from across Canada. The various adverse effects of antipsychotic drugs as well as their assessment and management are reviewed. Simple techniques for assessing adverse effects such as extrapyrimidal symptoms (EPS) are described. In some cases, adverse effects can be managed by dosage reduction and/or the use of adjunctive therapies such as antiparkinsonian agents and benzodiazepines. However, in some patients dose reduction carries the risk of symptom reemergence, while the commonly used adjunctive medications are associated with adverse effects of their own. Treatment-related side effects often require a reduction in dosage or a change in medication. Proper management can help encourage patient compliance and improve the outcome of antipsychotic treatment. The availability of the newer atypical antipsychotics offers another alternative, because they are associated with a much lower incidence of antipsychotic-induced side effects.

Delusional disorder in a boy with phenylketonuria and amine metabolites in the cerebrospinal fluid after treatment with neuroleptics

A case report of a 16-year-old boy with the classical form of phenylketonuria (PKU) and suffering from a delusional disorder is presented. He did not respond to a traditional antipsychotic medication but improved on an atypical antipsychotic, risperidone. The cerebrospinal fluid metabolites of the biogenic amines were measured and are also reported in the context of a recent interest in the ratios of these amine metabolites in schizophrenia. It is proposed that such dually diagnosed patients with PKU may provide a model in which to test the prevalent biogenic amine theories in psychiatric disorders.