The interaction of subjective experience and attitudes towards specific antipsychotic-related adverse effects in schizophrenia patients.

BACKGROUND: Discontinuation of antipsychotic drugs in schizophrenia patients is a major concern, since it results in relapse and re-hospitalizations. Non-adherence is strongly associated with negative-subjective response to antipsychotics, which is composed of the subjective experience of negative drug effects and attitude towards the treatment. OBJECTIVE: To investigate the elements of subjective experience and subjective attitude towards specific drug-related adverse effects, leading to a generally negative-subjective attitude towards antipsychotics. METHODS: Schizophrenia inpatients (n=84) were administered a questionnaire measuring attitude and experience on eight subscales: weight gain, sedation, sexual anhedonia, extra-pyramidal syndrome, affective flattening, excessive sleep, diminished sociability and metabolic syndrome. DAI-30 was used to measure attitude towards drugs, and PANSS to assess psychopathology. RESULTS: Weak correlation was found between subjective experience and attitude on most of the subscales. The only strong, albeit inverse, correlation between experience and attitude that was found was with regard to affective flattening, experienced by 37% of the sample, and it also predicted negative drug attitude as measured by the DAI-30, RR: 1.87 (95% CI: 1.06-3.3, df=1, χ(2)=4.525, P<0.05). CONCLUSION: Negative attitude towards most adverse drug effects did not correlate with personal experience. Drug-related affective flattening should be evaluated routinely, since experiencing it may predict negative attitude towards drugs, potentially leading to poor compliance and relapse.

The European Psychiatric Association (EPA) guidance on suicide treatment and prevention.

UNLABELLED: Suicide is a major public health problem in the WHO European Region accounting for over 150,000 deaths per year. SUICIDAL CRISIS: Acute intervention should start immediately in order to keep the patient alive. DIAGNOSIS: An underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential. TREATMENT: Existing evidence supports the efficacy of pharmacological treatment and cognitive behavioural therapy (CBT) in preventing suicidal behaviour. Some other psychological treatments are promising, but the supporting evidence is currently insufficient. Studies show that antidepressant treatment decreases the risk for suicidality among depressed patients. However, the risk of suicidal behaviour in depressed patients treated with antidepressants exists during the first 10-14 days of treatment, which requires careful monitoring. Short-term supplementary medication with anxiolytics and hypnotics in the case of anxiety and insomnia is recommended. Treatment with antidepressants of children and adolescents should only be given under supervision of a specialist. Long-term treatment with lithium has been shown to be effective in preventing both suicide and attempted suicide in patients with unipolar and bipolar depression. Treatment with clozapine is effective in reducing suicidal behaviour in patients with schizophrenia. Other atypical antipsychotics are promising but more evidence is required. TREATMENT TEAM: Multidisciplinary treatment teams including psychiatrist and other professionals such as psychologist, social worker, and occupational therapist are always preferable, as integration of pharmacological, psychological and social rehabilitation is recommended especially for patients with chronic suicidality. FAMILY: The suicidal person independently of age should always be motivated to involve family in the treatment. SOCIAL SUPPORT: Psychosocial treatment and support is recommended, as the majority of suicidal patients have problems with relationships, work, school and lack functioning social networks. SAFETY: A secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. TRAINING OF PERSONNEL: Training of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals.

Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia.

The beneficial effect of atypical antipsychotic drugs (APDs) in treatment-resistant schizophrenia patients has been attributed, mostly, to their relatively high serotonergic (5-HT)2 to dopaminergic (D)2 receptor blockade ratio. We hypothesized that a combination of typical APDs (D2 antagonists) and mianserin, a potent 5-HT2 antagonist, might also exert superior efficacy in this population. Eighteen inpatients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received, in a double-blind design, 30 mg/day mianserin (n = 9) or placebo (n = 9) in conjunction with typical neuroleptics [haloperidol (n = 9) or perphenazine (n = 9)]. Clinical status was evaluated before, during, and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores (17.6% versus 5.5%; P= 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P = 0.07). Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT2 blocker, such as mianserin, to typical antipsychotics. Our findings may further emphasize the contribution of enhanced 5-HT2 blockade to the 'atypicality' of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia.

Duffy antigen/receptor for chemokines (DARC): genotypes in Ashkenazi and non-Ashkenazi Jews in Israel.

Duffy genotypes were studied in Ashkenazi and non-Ashkenazi groups in Israel. The prevalence of the genotypes for the known polymorphic FY*A, FY*B, and FY*B(GATA-) alleles was similar in the two groups. The recently described FY*B(G298A) and FY*B(C265T) alleles were also found to be polymorphic. FY*B(G298A) was significantly more prevalent in the non-Ashkenazi group than in the Ashkenazi group (in 20% and 10% of FY*B, respectively). FY*B(C265T), which markedly diminishes the expression of Fy(b) antigen, was found in 3.5% of FY*B alleles, but only together with FY*B(G298A), consistent with previous suggestions that FY*B(C265T) occurred in the FY*B(G298A) allele. No difference in Duffy genotype distribution was found between schizophrenic and control groups. Duffy antigens are receptors for chemokines and bind Plasmodium vivax. Study of Duffy genotypes in additional populations might help in elucidating the possible functional significance of Duffy allele polymorphism.

Subjective effects of MDMA ('Ecstasy') on human sexual function.

Sexual function following 3,4-Methylenedioxymethamphetamine (MDMA, or 'Ecstasy') consumption was subjectively evaluated in 35 healthy recreational users (20 men and 15 women, aged 21-48 years) with regard to four major domains of sexual activity: desire, erection (lubrication in women), orgasm and satisfaction. Desire and satisfaction were moderately to profoundly increased by MDMA in more than 90% of subjects. Orgasm was delayed but perceived as more intense. Erection was impaired in 40% of the men. It seems that MDMA impairs sexual performance, in spite of enhancement of sexual desire and the perception of greater satisfaction.

Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study.

The purpose of this study was to investigate the efficacy of cyproheptadine, an antiserotonergic agent, in the treatment of neuroleptic-induced akathisia (NIA), as compared with propranolol, the current gold standard. In a double-blind trial, 30 patients with schizophrenia and NIA received either cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, followed by 3 days without any anti-NIA treatment. The Barnes Akahisia Scale, Simpson-Angus Extrapyramidal Effects Rating Scale, and Brief Psychiatric Rating Scale were used to assess the severity of NIA, parkinsonism, and psychosis, respectively. In both groups, the severity of NIA decreased significantly over time (cyproheptadine, -46%; propranolol, -42%), with no significant intergroup difference. The NIA symptoms worsened significantly when cyproheptadine and propranolol were discontinued. We conclude that cyproheptadine 16 mg/day is as effective as propranolol for the treatment of acute NIA. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity.

Sexual dysfunction in male posttraumatic stress disorder patients.

BACKGROUND: Previous studies have suggested that sexual dysfunction may be associated with posttraumatic stress disorder (PTSD). Yet such studies have not examined a full range of sexual functioning and have not accounted for the possibility that medication used to treat PTSD may contribute to sexual dysfunction. OBJECTIVE: The current study compares the various components of sexual functioning among three groups of males: (1) untreated PTSD patients (n = 15), (2) PTSD patients currently treated with selective serotonin reuptake inhibitor (SSRI) agents (n = 27) and (3) a group of normal controls (n = 49). METHODS: All participants completed an 18-item questionnaire for assessment of sexual functioning. Those with PTSD also completed the Impact of Events Scale and the Symptom Check List-90 (SCL-90). RESULTS: Untreated and treated PTSD patients had significantly poorer sexual functioning in all domains (desire, arousal, orgasm, activity and satisfaction) as compared to normal controls. Those treated with SSRI had greater impairment in desire, arousal and frequency of sexual activity with a partner. There was a high correlation between sexual dysfunction among the PTSD group and the anger-hostility subscale of the SCL-90. CONCLUSIONS: PTSD appears to be associated with pervasive sexual dysfunction that is exacerbated by treatment with SSRIs. PTSD may represent a heterogeneous syndrome. Patients with PTSD have a high rate of comorbid panic disorder, major depression and anxiety, and it could thus be argued that these comorbid disorders, rather than PTSD, accounted for the observed result. Future research aimed at understanding comorbidity and heterogeneity should help to illuminate the psychobiology of PTSD and eventually guide both medication and psychosocial treatments.

Sildenafil citrate (Viagra) treatment of sexual dysfunction in a schizophrenic patient.

A high frequency of sexual dysfunction occurs in treated and untreated patients with schizophrenia. Unfortunately, no effective therapy for this problem is currently available. We present a case of a 26-year-old patient with paranoid schizophrenia, who suffered from lack of desire and erection, and was successfully treated with sildenafil citrate (Viagra). This case illustrates the complex character of sexual dysfunction in male schizophrenia patients.

Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior.

OBJECTIVE: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients. METHOD: Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. RESULTS: Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes. CONCLUSIONS: Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.

The serotonin antagonist mianserin for treatment of serotonin reuptake inhibitor-induced sexual dysfunction in women: an open-label add-on study.

The aim of this study was to determine if the serotonin antagonist mianserin improves antidepressant-induced sexual dysfunction in women. The work was prompted by an earlier study of men by our team of researchers. The study population included 16 women aged 20-65 years undergoing treatment at a psychiatric outpatient clinic, who presented with sexual dysfunction subsequent to intake of a serotonin reuptake inhibitor (SRI) for depression. Sexual function (four domains) was evaluated by semistructured interviews before and after the administration of mianserin 15 mg/d for 3 weeks. The most prominent sexual dysfunction was anorgasmia. Clinically significant improvement was noted in all domains in two thirds of the patients, in most cases in the first or second week of treatment. None of the patients with panic disorder (PD) responded to mianserin, in contrast to those with affective disorder or obsessive compulsive disorder (OCD), indicating a possible relevance of the psychiatric diagnosis to mianserin effectiveness. There were no major adverse effects and no changes in the patients' stabilized psychiatric status. We conclude that mianserin is beneficial in reversing sexual function caused by SRI intake. Further large-scale, placebo-controlled studies are needed to confirm these findings.

Effect of amantadine on sexual dysfunction in neuroleptic-treated male schizophrenic patients.

Twelve male schizophrenic outpatients treated with neuroleptics took part in an open-label drug study to assess the impact of co-administration of amantadine hydrochloride (100 mg daily for 6 weeks) on sexual function. Amantadine improved the patients' scores in three out of four areas of sexual function: desire (p < 0.02), erection (p < 0.05), and satisfaction from sexual performance (p < 0.05); there was no change in ejaculatory function. Amantadine may be effective for improving sexual function in male schizophrenic patients receiving neuroleptic medication.

Senile degeneration and cognitive impairment in chronic schizophrenia.

OBJECTIVE: This study was an investigation of the role of Alzheimer-type senile degenerative abnormalities in the cognitive impairment of chronic schizophrenia. METHOD: The study group comprised 145 deceased elderly institutionalized psychiatric patients: 66 with schizophrenia, 26 with mood disorders, 36 with dementia, and 17 with other psychiatric diagnoses. The comparison group included 16 deceased elderly individuals without neurologic or psychiatric disease. Psychiatric diagnoses and cognitive status were established by standardized review of medical records. Neuritic senile plaques and neurofibrillary tangles were identified immunohistochemically and counted, by investigators blind to clinical information, in standardized regions of each brain. RESULTS: Of the subjects with schizophrenia, 68% had definite cognitive impairment, but only 8% satisfied neuropathological criteria for Alzheimer's disease. Among the schizophrenia subjects without Alzheimer's disease, definite cognitive impairment was associated with higher levels of plaques and tangles. The schizophrenia subjects without definite cognitive impairment had fewer plaques and tangles than the unimpaired nonpsychiatric subjects. CONCLUSIONS: Most cases of cognitive impairment in schizophrenia could not be attributed to Alzheimer's disease. An association of mild Alzheimer-type pathology with definite cognitive impairment was unique to schizophrenia. Enhanced sensitivity to the effects of aging on the brain may be a manifestation of diminished cognitive reserve in schizophrenia.

Elevated adhesiveness/aggregation of peripheral blood leukocytes in patients with major depression.

A simple slide test was used to determine the effects of major depression (MD) and heterocyclic antidepressants on leukocyte adhesiveness/aggregation (LAA) in the peripheral blood. Eighty subjects were categorized into four equal groups: untreated-MD patients, treated-MD patients, nondepressed patients treated with antidepressants and healthy controls. Significantly higher LAA values were observed both in untreated- and treated-MD patients, 13.8+/-1.7% and 13.5+/-1.9% respectively, compared to nondepressed-treated patients and healthy controls, 5.4+/-0.9% and 6.4+/-0.7% respectively (P < 0.0001). Increased LAA was associated with the depressive episode, was not affected by antidepressants and may potentially serve as a useful laboratory state marker for MD.

Mianserin, a 5-HT2a/2c and alpha 2 antagonist, in the treatment of sexual dysfunction induced by serotonin reuptake inhibitors.

Sexual dysfunction is commonly encountered in patients treated with antidepressants. The exact mechanism responsible for the sexual impairment is as yet unclear, although activation of the serotonergic system has been implicated. In the present study, we examined the effect of the 5-HT2a/2c and alpha 2 antagonist mianserin in the treatment of patients with sexual dysfunction induced by serotonin reuptake inhibitors (SRIs). Mianserin 15 mg was coadministered to 15 male subjects with new-onset sexual dysfunction who were under treatment with SRIs. Four major domains of sexual activity-desire, erection, orgasm, and satisfaction-were assessed once weekly for 4 weeks. At the end of the study, 9 of the 15 subjects reported a marked improvement in their sexual functioning, 2 reported partial improvement, and only 4 subjects showed no improvement at all. The beneficial effects were prominent in the areas of orgasm and satisfaction and were usually noted within the first and second week of mianserin treatment. The addition of mianserin to the treatment regimen was not associated with either improvement or worsening of the basic psychiatric clinical status. It appears that the coadministration of low-dose mianserin may be an additional option in the treatment of sexual dysfunction induced by SRIs.

Sulpiride adjunction to clozapine in treatment-resistant schizophrenic patients: a preliminary case series study.

Six chronic neuroleptic-resistant schizophrenic patients, partial responders to clozapine, were co-administered 600 mg/day of sulpiride (a selective D(2) dopaminergic antagonist) as an augmentation to clozapine (a relatively weak D(2) blocker), for 10 weeks, open-labeled. A remarkable reduction in positive and negative symptoms was observed in four of the six patients.

Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study.

BACKGROUND: We hypothesised that a combined regimen of clozapine, a relatively weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine. METHOD: Twenty-eight people with schizophrenia, previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression. RESULTS: The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterised by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and SAPS scores, respectively. CONCLUSIONS: A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine.

Lithium and male sexual function in affective patients.

The aim of the present study was to evaluate sexual function and behaviour in male patients who take lithium. Participants included 35 bipolar and schizoaffective men, aged 43.3 +/- 9.6 years, who were in euthymic state and were receiving lithium as the sole medical treatment. Eleven patients (31.4%) reported sexual dysfunction on at least two items of the sexual function questionnaire. Notable results were reduction in frequency of sexual thoughts and loss of erection during sex in 23 and 20% of patients, respectively. Difficulties in achieving and maintaining erections (ease of arousal) were reported in 14% of patients. Nevertheless, almost all patients reported preserved pleasure during sexual activity and were satisfied with their sexual performance. There was no difference in serum lithium levels in patients with and without sexual dysfunction. No statistical correlation was found between sexual function scores and serum lithium levels. Lithium therapy may impair desire and arousal, yet it does not appear to have a major impact on patient self-satisfaction or subjective sense of pleasure during sexual activity. The degree of sexual dysfunction as reported in the present study was not a source of distress to patients and did not cause noncompliance.

Acute effects of haloperidol on cerebral cortex blood flow in normal and schizophrenic subjects.

To evaluate the effects of neuroleptic medications on cerebral blood flow (CBF), cortical perfusion was quantified by the 133xenon technique in 8 unmedicated schizophrenics and 9 healthy controls before, and 1 and 3 hours after, administration of haloperidol (5 mg per os). At 3 hours, the normal subjects, but not schizophrenic patients, showed a significant increase in global mean perfusion (17 +/- 13%). Changes in CBF were not associated with plasma haloperidol levels or the presence of extrapyramidal side effects, and remained significant after controlling for pCO2. The lack of change in CBF in schizophrenic patients following acute haloperidol administration may be due to prior neuroleptic exposure, absence of anxiety, or other nonspecific factors, or may reflect a more fundamental feature of underlying pathophysiology in schizophrenia.

Trihexyphenidyl (Artane) abuse in schizophrenic patients.

Trihexyphenidyl (THP) and other anticholinergics are liable to abuse by schizophrenic patients. Data concerning the incidence and characteristics of the abusers are scarce. In the present study an evaluation of 214 consecutive admissions of schizophrenic patients revealed 14 THP abusers, an incidence of 6.5%. The demographic and clinical variables of the THP abusers were compared with a randomized control group of 28 schizophrenic patients using the four-dimensional factors of the BPRS (Brief Psychiatric Rating Scale). No significant differences were found in demographic variables and comorbidity for antisocial personality disorder and other substances abuse. On admission, a trend towards more negative symptoms was detected among abusers. At discharge abusers had significantly higher mean BPRS scores and higher scores on the dimensional factor of hostile-suspiciousness. The results suggest that THP abuse is not rare among schizophrenic patients who may abuse anticholinergic agents to relieve negative symptoms and/or drug-induced Parkinsonism, or alternatively for its non-specific stimulant effects, on account of worsening of positive symptoms.