Suicide risk assessment: time to think again?

This paper considers recent research on suicide risk assessment to support calls for a 'rethink' of our assessment of the patients in our care, along with the adoption of a more collaborative approach to care planning with service users who remain at risk of self-harm and in need of a plan for their safety.

Effect of fluoxetine on noradrenergic mediated growth hormone release: a double blind, placebo-controlled study.

Twelve patients with DSM-III-R major depressive illness were tested for growth hormone (GH) response to desipramine (DMI), a noradrenergic (NA) reuptake inhibitor. The response is mediated by NA alpha 2 receptors. They were then randomly assigned to treatment under double-blind conditions with either fluoxetine, the highly selective serotonin reuptake inhibitor or placebo. After 4 weeks they were retested. Fluoxetine but not placebo was effective in promoting recovery in four of the six patients treated. Patients treated with fluoxetine showed a significant decrease in DMI-mediated GH release irrespective of therapeutic outcome. This is consistent with marked alteration of NA function and raises questions as to the selectivity of fluoxetine.

Specificity of the pyridostigmine/growth hormone challenge in the diagnosis of depression.

Acetylcholine is a neurotransmitter that has been implicated in the pathophysiology of major depression. This is supported by the enhanced growth hormone (GH) release in response to pyridostigmine (PYD) challenge in depressed subjects relative to healthy comparison subjects. The aim of this study is to examine the specificity of the PYD/GH challenge in the diagnosis of depression. Pyridostigmine 120 mg orally, was administered to a total of 116 physically healthy subjects. Growth hormone responses were studied in 38 patients with (DSM-III-R) major depression, 13 subjects with panic disorder, 9 subjects with schizophrenia, 10 recently detoxified alcoholics, and a comparison group of 46 healthy volunteers. Mean delta GH (the difference between basal and maximal GH following PYD) was significantly greater than comparison subjects in patients with major depression. Responses observed in patients with schizophrenia and alcohol dependence syndrome did not differ from the comparison group. Those patients with panic disorder and a high Hamilton depression score had an enhanced delta GH. The sensitivity of the PYD/GH test was 63% for major depression. These results indicate that the PYD/GH test may help distinguish depression from schizophrenia, alcohol-dependence syndrome, or panic disorder with a low Hamilton depression score.

Neuroendocrine evidence that clozapine's serotonergic antagonism is relevant to its efficacy in treating hallucinations and other positive schizophrenic symptoms.

OBJECTIVE: The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia. METHOD: Prolactin responses to the 5-HT releasing agent d-fenfluramine were measured in two groups of 10 schizophrenic subjects. The first group was tested twice, before and after a mean of 10 weeks of clozapine treatment. The second group was tested after a mean of 20 months of clozapine treatment. RESULTS: The prolactin response was significantly blunted in these 20 patients treated with clozapine. There was a significant positive correlation between d-fenfluramine-evoked prolactin release and the overall positive symptom score and the hallucination and delusion subscores of the Scale for the Assessment of Positive Symptoms. CONCLUSIONS: Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving clozapine monotherapy for up to 20 months were correlated with reductions in positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's efficacy in alleviating hallucinations and other positive schizophrenic symptoms.

Central serotonergic hyperresponsivity in late-onset Alzheimer's disease.

The prolactin response to oral d-fenfluramine (30 mg) was measured in nine patients with late-onset Alzheimer's disease and in an elderly comparison group. The serotonin-mediated prolactin response was significantly greater in the patients with Alzheimer's disease than in the comparison group. This finding suggests that central serotonin responsivity is greater in Alzheimer's disease.

Elevated growth hormone responses to pyridostigmine in obsessive-compulsive disorder: evidence of cholinergic supersensitivity.

The growth hormone response to the acetylcholinesterase inhibitor pyridostigmine was measured in nine normothymic outpatients who met DSM-III-R criteria for obsessive-compulsive disorder. The responses were significantly elevated when compared to those found in a healthy comparison group (N = 9). The data suggest that cholinergic supersensitivity is present in obsessive-compulsive disorder.

Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia.

OBJECTIVE: Although there is evidence from postmortem studies suggestive of deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) in schizophrenia, no direct in vivo evidence has been obtained to date. The authors used single photon emission computed tomography (SPECT) with iodine-123-labeled iomazenil ([123I]iomazenil), a radioligand that selectively binds with high affinity to the benzodiazepine subunit of the GABAA receptor complex in the human brain, to investigate the presence of benzodiazepine receptor abnormalities in the cerebral cortex of living subjects with schizophrenia. METHOD: Dynamic [123I]iomazenil SPECT was performed in 15 patients (14 patients with DSM-III-R schizophrenia and one with schizophreniform disorder) and 12 healthy subjects over a period of 2 hours. The time-integral method was used to generate ratios of "specific" to "nonspecific" [123I]iomazenil binding at equilibrium for several cortical regions. RESULTS: No overall between-group differences in benzodiazepine receptor binding were found, but significant correlations emerged between the severity of schizophrenic symptoms and [123I]iomazenil binding in limbic cortical regions: positive symptom scores were negatively correlated with benzodiazepine receptor binding in the left medial temporal region, and negative symptoms were inversely related to receptor binding in the medial frontal region. These correlations were not significant when a Bonferroni correction for multiple comparisons was applied. CONCLUSIONS: These preliminary results are consistent with previous research implicating limbic cortical regions in the pathophysiology of schizophrenia, suggesting that reduced inhibitory GABAergic tone in these areas may contribute to the appearance of schizophrenic symptoms.

Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group.

BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.

BAP/SKB Young Psychopharmacologist Award Towards a neuroendocrinology of obsessive-compulsive disorder.

Neuroendocrine research has made an important contribution to the understanding of psychiatric illness in vivo. This review is a summary of the recent neuroendocrine studies on obsessive-compulsive disorder (OCD) patients carried out at the Departments of Psychiatry at Trinity College Medical School and St. Patrick's Hospital, Dublin, Ireland. We found that both serotonergic and cholinergic abnormalities were present in OCD, while noradrenergic responsivity and hypothalmic-pituitary axis function were normal. The data suggests that OCD may have a unique neuroendocrinology.

Buspirone induced prolactin responses in obsessive-compulsive disorder (OCD): is OCD a 5-HT2 receptor disorder?

Buspirone (BUSP) is a serotonergic (5-HT) agonist with activity at the 5-HT1A receptor. The BUSP induced prolactin (PRL) response was examined in 10 patients with a DSM IIIR diagnosis of obsessive-compulsive disorder (OCD). The results were compared with PRL responses to BUSP found in 10 age and sex matched healthy controls. The results suggest that the 5-HT1A receptor dysfunction may not be involved in the pathophysiology of OCD. The authors review the literature and consider the hypothesis that in OCD a complex interaction of other 5-HT receptor sub-types may be occurring, possibly with dysfunction primarily of the 5-HT2 receptors.

Risperidone is associated with blunting of D-fenfluramine evoked serotonergic responses in schizophrenia.

The high 5-HT affinity of some atypical antipsychotic agents is thought to contribute to their clinical efficacy. We examined central 5-HT responses in two groups of ten schizophrenic patients by measuring serum prolactin and cortisol responses to the neuroendocrine challenge D-fenfluramine. One group of patients with schizophrenia was tested after a 2-week neuroleptic free period. A similar group were tested after a mean of 12 weeks treatment with the atypical antipsychotic risperidone. A significant elevation of baseline serum prolactin levels, consistent with dopaminergic antagonism was seen after risperidone treatment. Significantly reduced 5-HT mediated serum prolactin responses were seen in risperidone treated patients. D-fenfluramine evoked serum prolactin responses were positively correlated with positive but not negative schizophrenic symptoms for all 20 patients. Risperidone treatment was associated with a significant functional in-vivo 5-HT antagonism similar to clozapine. 5-HT antagonism may contribute to the efficacy of risperidone against positive schizophrenic symptoms.

Gender and age differences in the growth hormone response to pyridostigmine.

Thirty healthy subjects 12 males and 18 females were given the acetylcholinesterase inhibitor pyridostigmine (120 mg) orally. The growth hormone (GH) response was measured as the maximum GH level post-pyridostigmine relative to baseline. Twenty-six subjects increased their GH level in response to pyridostigmine. Responses in females were considerably greater than those in males and correlated closely with serum oestradiol levels. Overall there was a significant negative correlation between GH response and age.

Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography.

We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD.

Schizophrenic auditory hallucinations are associated with increased regional cerebral blood flow during verbal memory activation in a study using single photon emission computed tomography.

Single photon emission tomography with split-dose technetium-99m-d, l-hexamethyl-propylene amine oxime was used to measure regional cerebral blood flow (rCBF) during a memory-activation paradigm in a group of 18 medicated DSM-III-R schizophrenic patients. The relationship between clinical features of schizophrenia and rCBF patterns was examined. Increased blood flow to the left basal ganglia was revealed during activation in patients reporting hallucinations in the previous month, a finding that was not influenced by medication dose or other confounding variables. This result adds to previous functional imaging studies that have related basal ganglia abnormalities to hallucinatory phenomena and suggests that left basal ganglia hyperactivity may be relevant to an internal monitoring deficit responsible for the appearance of those symptoms in schizophrenia.

Risperidone compared with olanzapine in a naturalistic clinical study in Ireland: a cost analysis.

BACKGROUND: Risperidone and olanzapine are thought to have similar clinical effects. This study was designed to compare costs of treatment. AIM: To compare costs of treatment with risperidone or olanzapine in a naturalistic setting. METHOD: The Irish Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme was a retrospective review of medical notes and prescription charts in 396 inpatients with schizophrenia or schizoaffective disorder. The main outcome measure was cost of inpatient drug treatment. RESULTS: There was no statistical difference in length of hospital stay between risperidone-treated and olanzapine-treated patients (mean duration of stay 37.8 and 40.5 days, p=0.90). Mean+/-SD doses of risperidone and olanzapine were 4.2+/-2.1 mg/day and 12.9+/-5.0 mg/day, respectively. Average daily cost of all inpatient drugs was significantly higher for olanzapine than for risperidone (i.e. IEP5.61 [7.12] vs IEP3.38 [4.29]; p<0.0001), as was mean total costs of all inpatient drugs (i.e. IEP114.8 [145.8] vs IEP62.0 [78.7]; p<0.0001). This partly reflected the mean, non-significant, longer treatment duration for olanzapine compared with risperidone (mean 30.0 vs 26.4 days; p=0.27). Concomitant neuroleptic use was similar for both groups (71% risperidone, 73% olanzapine; p=0.54). CONCLUSION: Risperidone was associated with significantly lower drug treatment costs.

Parent-child relationships in gender identity disorder.

OBJECTIVE: To describe the relationship between parents with gender identity disorder (GID) and their child(ren) as described by the parent and to understand how being a parent affects transitioning from one gender to the other. METHODS: Fourteen parents with GID underwent a semi-structured interview and completed the Index of Parental Attitudes (IPA). An IPA score of greater than 30 indicates parent­child relationship difficulties (range 0­100). The authors also conducted the SCID-I to establish other Axis I disorders. RESULTS: We assessed 12 male to female and two female to male parents with GID residing in Ireland. In total, 14 GID parents had 28 children. Three children had no relationship with their GID parent. The other 25 children, as reported by the parent, had good relationships with their children. In addition, these 25 children average score IPA score was 6.4 (range 0­25). Twelve GID parents (86 %) believed that being a parent had no effect on their desired level of transitioning, while two were influenced not to transition. Eleven GID parents (79 %) reported that being a parent had increased the time taken to commence transitioning, two have stopped transitioning altogether, while one cited no effect on time. CONCLUSION: Parents with GID report positive relationships or no relationship with their children and the IPA revealed no clinical problems. Being a parent can prolong transitioning time in people with GID and can affect overall achieved level of transitioning.

A structured process for reviewing the operation of the Mental Health Act 2001 in an Irish mental health service.

This paper provides a description of a structured template which allows review of the operation of the Mental Health Act 2001 at St Patrick's Mental Health Services (incorporating St Patrick's University Hospital, St Edmundsbury Hospital and Willow Grove Adolescent Unit). These structured processes were implemented to ensure rigorous monitoring of all clinical governance activities associated with adherence to the Mental Health Act (MHA) 2001. The paper describes in detail the information contained in the St Patrick's Mental Health Services dashboard for 2012. The dashboard displays the key performance indicators that are monitored and the paper describes how these were reviewed by the Hospital's Clinical Governance Committee on a weekly basis for the three approved centres. The dashboard has also been used by the Clinical Governance Committee to provide ongoing education and engagement with staff in order to improve the operation of the MHA 2001. The use of this structured monitoring process has allowed the hospital to measure adherence to the MHA 2001 and also to measure activities that impact directly on the care and treatment of patients detained under the Act. The use of structured monitoring tools (i.e. the dashboard) to review the operation of the MHA 2001 allows for coherent observation of key events and issues which can cause concern in terms of the operation of the Act.

Orofacial dyskinesia and the alcohol dependence syndrome.

A total of 52 patients with a DSM-III-R diagnosis of alcohol dependence syndrome underwent successful detoxification. Two to three weeks later they were examined for the presence of abnormal involuntary movements and rated with the abnormal involuntary movements scale (AIMS). They were also assessed with subtests from the Wechsler Adult Intelligence Scale (WAIS-R), namely, visual reproduction from memory, digit symbols substitution and the vocabulary test. Twenty-nine had evidence of orofacial dyskinesia and the presence of such movements was strongly associated with visuospatial deficits.

Enhanced growth hormone responses to pyridostigmine challenge in patients with panic disorder.

BACKGROUND: Panic disorder is associated with neuroendocrinological abnormalities, some of which overlap with those seen in major depression. To date, there has been little assessment of the role of cholinergic mechanisms in this disorder. METHOD: Sixteen patients with DSM-III-R panic disorder and an age and gender-matched comparison group were administered 120 mg of the acetylcholinesterase inhibitor pyridostigmine. Growth hormone (GH) responses over a three-hour period were monitored. RESULTS: Mean delta GH, the difference between basal and the maximum pyridostigmine levels, was significantly greater in patients with panic disorder than in the comparison group. CONCLUSIONS: This may reflect increased cholinergic responsivity in panic disorder.