Integration of mental health comorbidity in medical specialty programs in 20 countries.

METHODS: A systematic analysis was performed of the medical specialization academic programs of 20 different countries to establish which medical specialties take into account mental health issues in the specialty curricular design and which mental health content these programs address. The criteria that were explored in the educational programs include: 1) name of the medical specialties that take into account mental health content in curriculum design, 2) name of the mental health issues addressed by these programs. After independent review and data extraction, paired investigators compared the findings and reached consensus on all discrepancies before the final presentation of the data. Descriptive statistics evaluated the frequency of the data presented. RESULTS: Internal medicine, family medicine, neurology, pediatrics and geriatrics were the specialties that included mental health topics in their programs. In four countries: Bangladesh, Serbia, the Netherlands and France, 50%of all graduate specialty training programs include mental health content. In ten countries: Germany, Sweden, the United Kingdom, Mexico, Belgium, India, Russia, Canada, Israel and Spain, between 20% and 49% of all graduate specialty training programs include mental health content. In six countries - Brazil, Chile, Colombia, Croatia, Kenya, and the United States-less than 20% of all graduate specialty training programs include mental health content. DISCUSSION: The proposal that we have made in this article should be taken into account by decision-makers, in order to complement the different postgraduate training programs with mental health issues that are frequently present with other physical symptoms. It is not our intention that the different specialists know how to treat psychiatric comorbidities, but rather pay attention to their existence and implications in the diagnosis, evolution and prognosis of many other diseases. The current fragmentation of medicine into ever finer specialties makes the management of comorbidity ever more difficult: a reorientation of post- graduate training might improve the situation.

Very Low-Dose Mirtazapine (7.5 mg) in Treatment of Acute Antipsychotic-Associated Akathisia.

BACKGROUND: Some evidence suggests that off-label use of mirtazapine (15 mg) is effective in treatment of acute antipsychotic-associated akathisia (AAA). We analyzed whether a lower dose of mirtazapine (7.5 mg) maintained its antiakathisia properties while exhibiting better tolerability in patients with schizophrenia and mood disorders who developed acute AAA. METHODS: Medical charts were retrospectively evaluated for 12 patients with AAA. All scored at least 2 (mild akathisia) on the Barnes Akathisia Rating Scale (BARS) and were treated with mirtazapine (7.5 mg) for a mean of 10.3 days. RESULTS: There was a statistically significant decrease in the BARS subjective, distress, and global (P < 0.01 to P < 0.001), but not objective (P = 0.63), subscales. Five participants (41.6%) fulfilled the predefined criterion of response, a decrease of at least 2 points on the BARS global subscale. The positive antiakathisia effect of mirtazapine was observed predominantly in aripiprazole-treated patients. Mirtazapine (7.5 mg) was well tolerated, and no clinically significant adverse effects, primarily drowsiness or increased appetite, were reported. CONCLUSIONS: A large-scale controlled evaluation is warranted to substantiate clinical utility of off-label use of mirtazapine (7.5 mg) for patients with AAA.

Standards of care for obsessive-compulsive disorder centres.

In recent years, many assessment and care units for obsessive-compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a standards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries.

Treatment of Antipsychotic-Related Akathisia Revisited: The Role of Serotonin 2A Receptor Antagonists.

Akathisia remains a prevalent, clinically significant, and therapeutically challenging adverse event associated with antipsychotic treatment. Compelling evidence supports therapeutic efficacy and clinical utility of agents with marked serotonin 2A receptor antagonism, primarily low-dose mirtazapine, as an effective and well-tolerated antiakathisia treatment.

Global functional connectivity deficits in schizophrenia depend on behavioral state.

Schizophrenia is a devastating psychiatric illness characterized by deterioration of cognitive and emotional processing. It has been hypothesized that aberrant cortical connectivity is implicated in the disease (Friston, 1998), yet previous studies of functional connectivity (FC) in schizophrenia have shown mixed results (Garrity et al., 2007; Jafri et al., 2008; Lynall et al., 2010). We measured FC using fMRI in human schizophrenia patients and healthy controls during two different tasks and a rest condition, and constructed a voxel-based global FC index. We found a striking FC decrease in patients compared with controls. In the task conditions, relatively weaker FC was specific to regions of cortex not active during the task. In the rest condition, the FC difference between patients and controls was larger and allowed a case-by-case separation between individuals of the two groups. The results suggest that the relative reduction of FC in schizophrenia is dependent on the state of cortical activity, with voxels not activated by the task showing higher levels of FC deficiency. This novel finding may shed light on previous reports of FC in schizophrenia. Whether this neural characteristic is related to the development of the disorder remains to be established.

Age-of-onset of schizophrenic and obsessive-compulsive symptoms in patients with schizo-obsessive disorder.

Obsessive-compulsive symptoms (OCS) are prevalent, persistent, clinically significant phenomena in schizophrenia. To facilitate the understanding of their temporal interrelationship, we assessed age-of-onset of schizophrenic and obsessive-compulsive symptoms among 133 patients admitted to Tirat Carmel Mental Health Center (Israel) during the years 1999-2010 who met DSM-IV criteria for both schizophrenic disorder and obsessive-compulsive disorder (OCD). The mean age-of-onset of the first clinically significant OCS was significantly earlier than the mean age-of onset of the first psychotic symptoms. An earlier onset of OCS was detected in men, but not in women. In sixty-four of 133 patients OCS preceded the first psychotic symptoms, in 37 patients OCS followed them, and in 32 patients OCS and psychotic symptoms occurred simultaneously. A sub-analysis of 52 first-episode schizophrenia patients revealed that OCS emerged approximately 3 years earlier than psychotic symptoms. Notably, schizo-obsessive patients had earlier mean age-of-onset of first psychotic symptoms than a comparative group of 113 non-OCD schizophrenia patients matched for age, gender and number of hospitalization. Earlier emergence of OCS than schizophrenic symptoms in schizo-obsessive patients suggests that they are independent of psychosis and are not consequent to schizophrenia. In addition, the presence of OCS seems to modify clinical features of schizophrenia accounting for earlier onset of first psychotic symptoms, however a replication of these findings is needed.

Obsessive-compulsive symptoms in schizophrenia: implications for future psychiatric classifications.

Although obsessive-compulsive symptoms are not considered primary features, they are prevalent, independent of psychosis, and substantially modify clinical characteristics, course, treatment and prognosis of schizophrenia. The authors highlight the clinical significance of obsessive-compulsive symptoms in schizophrenia, provide diagnostic criteria for "schizo-obsessive" patients and address future directions for research.

Adenosine A2A-receptor antagonism and pathophysiology of Parkinson's disease and drug-induced movement disorders.

Parkinson's disease and drug-induced movement disorders (DIMDs) have commonalities in etiology based on impaired dopamine-based neurotransmission. Adenosine A(2A)-receptor antagonism may provide a new mechanism through which these disorders can be managed. In the motor circuit, tonic output from the globus pallidus and substantia nigra regulates movement via opposing excitatory and inhibitory inputs to the cerebral cortex through the direct and indirect pathways. Increased activity of the direct pathway increases movement via an inhibitory effect on thalamocortical projection neurons; increased activity of the indirect pathway has the opposite effect. Regulation of these pathways is mediated primarily by reciprocal inhibitory interactions between dopamine and adenosine receptors on neurons of these pathways. Adenosine A(2A) receptors are colocalized with dopamine D(2) receptors on the indirect pathway neurons, with A(2A) activation opposing the effect of D(2) activation. The A(2A) receptors' role in the pathophysiology of Parkinson's disease and DIMDs is evidenced by the upregulation of A(2A) receptors in patients with Parkinson's disease and patients receiving long-term administration of dopamine blockers. Further, A(2A)-receptor antagonists are effective in reversing parkinsonian motor deficits and extrapyramidal symptoms in animal models of Parkinson's disease and DIMDs. Understanding the role of A(2A)-receptor antagonism in the pathophysiology of Parkinson's disease and DIMD has therapeutic implications.

Obsessive musical hallucinations in a schizophrenia patient: psychopathological and FMRI characteristics.

Obsessive-compulsive symptoms (OCS) are relatively common and clinically significant phenomena in schizophrenia patients, suggesting the existence of a separate schizo-obsessive subgroup of the disorder. Although a majority of schizo-obsessive patients have typical ego-dystonic OCS, a meaningful proportion exhibits diagnostically challenging psychopathological phenomena, psychotic in content and obsessive in form. We report the clinical and functional magnetic resonance imaging characteristics of a schizophrenia patient who developed auditory hallucinations with musical content and obsessive in form. We suggest that "obsessive musical hallucinations", that integrate both psychotic and obsessive-compulsive disorder (OCD)-related features, may be mediated by the brain networks believed to be involved in OCD and in auditory musical hallucinations.

Quetiapine for Bipolar Depressive Episode in Obsessive-Compulsive Disorder Patients Maintained on Selective Serotonin Reuptake Inhibitor Treatment.

OBJECTIVES: A meaningful proportion of patients with obsessive-compulsive disorder (OCD) develop symptoms of bipolar depression (BP-D). In the present investigation, we aimed to determine whether quetiapine is efficacious in OCD patients who despite continuous treatment with a selective serotonin reuptake inhibitor developed an acute episode of BP-D. METHODS: We analyzed 68 charts of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition OCD patients from our outpatient clinic and identified 15 patients who in addition met Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for bipolar II disorder, depressive episode. Eleven (7 men and 4 women, aged 24-54 years) patients for whom quetiapine was added to treat the index episode of BP-D were included. Treatment response was assessed retrospectively and defined as a score of "much improved" or "very much improved" on the Clinical Global Impression-Improvement scale. RESULTS: Quetiapine was added for treatment of BP-D in a dose range of 150 to 400 mg (mean, 273 mg). Eight (73%) of the 11 study patients fulfilled the criterion of response, that is a score of "much improve" (4 patients) and "very much improved" (4 patients) on the Clinical Global Impression-Improvement scale. Notably, quetiapine was associated with additional improvement of OCD symptoms in 6 of 8 study responders. Quetiapine was well tolerated. The most frequently detected side effects were drowsiness (5 patients), constipation (4 patients), and orthostatic hypotension (2 patients). CONCLUSIONS: The revealed beneficial effect of quetiapine addition for acute episode of BP-D in OCD patients maintained on selective serotonin reuptake inhibitor treatment merits further controlled investigation.

Beneficial effect of quetiapine monotherapy in patients with bipolar depression and comorbid obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a prevalent and clinically significant comorbid condition in patients with bipolar disorder. Treatment of bipolar disorder/OCD patients is challenging. We report the results of an open-label, short-term, prospective investigation of quetiapine monotherapy in 16 patients (three men and 13 women, aged 18-56 years) hospitalized for acute bipolar depression who in addition met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for OCD. The participants were treated with quetiapine in a dose range of 150-600 mg (mean 347 mg) for a mean duration of 4.3 ± 1.4 weeks (range 3-7 weeks). Eleven (68.8%) of the 16 study participants fulfilled the predefined criteria for response, namely a score of 'very much improved' (four patients) and 'much improved' (seven patients) on the Clinical Global Impression - Improvement scale. Treatment with quetiapine was associated with a statistically significant decrease from baseline in the relevant rating scales for the assessment of depressive, manic and OCD symptoms. Quetiapine was well tolerated. The most frequently reported side effects were sedation, orthostatic hypotension and constipation. Durability of the positive therapeutic effect of quetiapine monotherapy in patients with bipolar disorder/OCD comorbidity and the necessity for subsequent augmentation with anti-OCD agents need to be addressed in future controlled studies.

Rate of OCD and sub-threshold OCD in bipolar disorder patients with first depressive episode.

Evidence indicates that obsessive-compulsive disorder (OCD) co-occurs with bipolar disorder (BD) at a higher rate than in the general population. Although there is a preliminary indication of a predominant aggregation of OCD in BD patients with bipolar depression (BP-D), no explicit evaluation has previously been undertaken. Using the Structured Clinical Interview for DSM-5 Axis-I disorders and appropriate rating scales, seventy-three BD patients experiencing their first depressive episode were screened for OCD and subthreshold OCD. Nineteen (26%) of the 73 participants in addition to BP-D also met DSM-5 criteria for OCD and 17 (23.2%) patients met criteria for sub-threshold OCD. No differences in demographic and clinical variables evaluated in the study were found between the BP-D patients with and without OCD. Limitations of the study included a relatively small sample size, cross-sectional design and inclusion of only hospitalized BP-D patients. Additional studies are warranted to better define the longitudinal course of comorbid BP-D/OCD, treatment approaches and outcomes of this challenging patient population. Explicit prospective comparison of the rate of DSM-5 OCD and subthreshold OCD in depressive versus manic episodes of bipolar disorder within the same patient is justified.

Acute antipsychotic-induced akathisia revisited.

Akathisia remains one of the most prevalent and distressful antipsychotic-induced adverse events. Effective and well-tolerated treatment is a major unmet need in akathisia that merits a search for new remedies. Accumulating evidence indicates that agents with marked serotonin-2A receptor antagonism may represent a new class of potential anti-akathisia treatment.

Treatment of Antipsychotic-Induced Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists.

Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced akathisia (AIA). Surprisingly, the evidence for its anti-akathisia effect is modest. Propranolol's side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in akathisia and warrants a search for new anti-akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-akathisia remedies. Among these agents, low-dose mirtazapine (7.5 mg or 15 mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.

Effect of the selective norepinephrine reuptake inhibitor reboxetine on cognitive dysfunction in schizophrenia patients: an add-on, double-blind placebo-controlled study.

The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia patients, and the NE transporter represents a putative target for cognitive enhancing therapy. In a double-blind placebo-controlled study we evaluated the effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10 mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test were used to assess selective cognitive functions at baseline and endpoint (6 weeks). Clinical assessment was also performed. No between-group differences were found in neurocognitive tests, suggesting that reboxetine did not significantly change patients' cognitive performance compared to placebo. Reboxetine was well-tolerated and did not interfere with the therapeutic effect of olanzapine. Long-term studies using higher reboxetine dosages and alternative NRIs (e.g., atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in patients with schizophrenia and other disorders associated with cognitive impairments.

Comparison of clinical characteristics, co-morbidity and pharmacotherapy in adolescent schizophrenia patients with and without obsessive-compulsive disorder.

A substantial proportion of adolescent schizophrenia patients exhibit obsessive-compulsive symptoms/disorder (OCS/OCD). In the present study we sought to provide a clinical characterization of adolescent schizo-obsessive patients. A consecutive sample of 22 adolescent patients (age 13-18 years) who met DSM-IV criteria for both schizophrenia and OCD was compared with 22 non-OCD schizophrenia patients matched for age, gender and number of hospitalizations. The Structured Clinical Interview for DSM-IV Axis I psychiatric disorders (SCID-I), the Scale for the Assessment of Positive (SAPS) and Negative (SANS) Symptoms, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression (CGI) were used. We found that schizo-obsessive patients had earlier age at onset of schizophrenia symptoms, had more OCD spectrum disorders, primarily tic disorders, but did not differ in severity of schizophrenia symptoms from non-OCD schizophrenia patients. In a majority of the schizo-obsessive patients, OCS preceded or co-occurred with the onset of schizophrenia and did not correlate with schizophrenic symptoms. As expected, more schizo-obsessive patients than their non-OCD counterparts were treated with adjunctive anti-obsessive agents. These findings indicate that clinical characteristics of adolescent schizo-obsessive patients are generally similar to those previously revealed in their adult counterparts. The neurobiology underlying the co-occurrence of the OC and schizophrenia symptoms merits further evaluation.

Clinical characteristics of schizotypal-related obsessive-compulsive disorder.

In this study we compared 15 patients with DSM-IV obsessive-compulsive disorder (OCD) and schizotypal personality disorder (SPD) and 31 non-SPD OCD patients. OCD-SPD patients had poorer insight, more negative symptoms, lower functioning, more antipsychotic augmentation and more first-degree relatives with schizophrenia-spectrum disorders. A distinct clinical phenotype of OCD associated with SPD should be considered when investigating etiopathogenetic mechanisms.

Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study.

RATIONALE: Search for safe and effective strategies to diminish weight gain associated with second generation antipsychotics (SGAs) is imperative. In the present study, we sought to replicate our preliminary findings, which indicated that coadministration of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. MATERIALS AND METHOD: Fifty-nine patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in this randomized double-blind study. Reboxetine (4 mg/day; 31 patients) or placebo (29 patients) was coadministered with olanzapine (10 mg/day) for 6 weeks. Analysis was by intention-to-treat. RESULTS: Nine patients in each group prematurely discontinued the trial. Olanzapine/reboxetine-treated patients showed a significantly lower increase in body weight (mean = 3.31 kg, SD = 2.73) than their olanzapine/placebo-treated counterparts (mean = 4.91 kg, SD = 2.45). Significantly fewer olanzapine/reboxetine-treated patients gained at least 7% of their initial weight, the cutoff for clinically significant weight gain (6 [19.4%] of 31 patients vs 13 [46.4%] of 28 patients). Seven (22.6%) olanzapine/reboxetine-treated patients compared to only one patient (3.6%) in the olanzapine/placebo group revealed no weight change or even modest weight loss. Appetite increase was significantly lower in the olanzapine/reboxetine than olanzapine/placebo group and was correlated with attenuation of weight gain. Reboxetine addition was safe and well tolerated. CONCLUSIONS: The results confirm that coadministration of reboxetine promotes a clinically meaningful attenuation of olanzapine-induced weight gain in schizophrenia patients. If substantiated in long-term studies, along with behavioral management and diet counseling, reboxetine may have a clinical utility in controlling SGA-induced weight gain.