Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic and clinical evolution at follow up.

The study reports a follow-up assessment of 48 patients with concomitant drug abuse at the first admission for psychosis. We focused on the diagnostic distinction between primary psychosis with concomitant drug abuse and drug induced psychosis, to observe whether the diagnoses are stable over time and whether the clinical course significantly differs. The study examined 25 primary psychotic disorder with comorbid drug abuse and 23 drug-induced psychotic disorder patients. Diagnostic and psychopathological assessments were made at baseline and at follow-up. Mean follow-up period was 4.96 years. Patients with comorbid Drug Abuse exhibited higher scores in the item Unusual Content of Thought at baseline than drug-induced psychotic disorder patients: 5.48 vs 4.39 while the two patients groups did not differ in any of the BPRS items evaluated at follow-up. The primary psychosis with comorbid drug abuse and the substance induced psychosis groups were similar regarding diagnostic stability, and a diagnosis of schizophrenia at follow-up occurred similarly. There was no evidence that Drug Induced psychotic patients' symptoms tend to improve more after cessation of drug abuse. An earlier age of onset was found in primary psychotic patients, particularly for patients diagnosed as affected by schizophrenia at follow up. These results might reflect the uncertainty of the distinction between Primary and Drug Induced Psychosis and the difficulties in applying the DSM IV-TR criteria for diagnosing comorbid drug use disorders and psychotic disorders.

Paliperidone for the treatment of schizophrenia and schizoaffective disorders - a drug safety evaluation.

INTRODUCTION: Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER) oral formulation and a long-acting injectable paliperidone palmitate (PP) formulation. Paliperidone has demonstrated efficacy in the reduction of acute schizophrenia symptoms and clinical benefits were maintained also in the long-term treatments. Paliperidone ER and PP are generally well tolerated with a predictable adverse event profile. Areas covered: Data from studies evaluating safety and tolerability in the acute and maintenance treatment of schizophrenia with paliperidone are reviewed. The reported treatment-emergent adverse events of these formulations are discussed. Expert opinion: In the treatment of schizophrenia and schizoaffective disorders the safety profile has a central role because it can enhance patient compliance. In fact treatment-emergent adverse events are one of the main causes of discontinuation in these patients. In particular the main limitation in the administration of paliperidone could be represented by the onset of hyperprolactinemia (especially in women) and of mild parkinsonism. Paliperidone has a high impact on current long-term drug strategies, especially given the new 3 month long-acting injectable formulation of PP.

Clinical and neuropsychological correlates of major depression following post-traumatic brain injury, a prospective study.

OBJECTIVES: Major depression disorder (MDD) is the most frequent psychiatric complication after traumatic brain injury (TBI), with a prevalence of 14-77%. The aim of this study was to analyse the psychiatric sequelae of TBI, and to identify the neuropsychological and psychopathological correlates of post-TBI MDD in order to highlight their differences from those of primary MDD. METHODS: This was a longitudinal, prospective, case-control study. Sixteen patients with closed brain injury, and a lesion revealed by computed tomography (CT), were recruited and were evaluated one (T1), three (T3) and six (T6) months after discharge from Neurosurgery Department; the controls were six patients with MDD. The psychiatric symptoms were evaluated using brief psychiatric rating scale (BPRS), Hamilton depression rating scale (HRSD), Beck depression inventory scale (BDI), Hamilton anxiety rating scale (HRSA), global assessment of functioning (GAF) and instrumental activity of daily living (IADL). Neuropsychological profiles were assessed by using neuropsychological tests, focused on memory and frontal-executive functioning. RESULTS: At T1, MDD was observed in 10 cases (62.5%), a manic episode in 12.5%, and post-traumatic stress disorder in 6.5%. At T3 and T6, MDD was diagnosed in, respectively, eight (50%) and six cases (37.5%). Post TBI MDD had less severe depressive symptoms, showed greater social isolation and hostility and more cognitive deficits in comparison with the control group. CONCLUSIONS: MDD is a frequent TBI complication. Patients with post-TBI MDD have a specific psychopathological profile characterised by a less severe depressive symptomatology and a neuropsychological pattern that is significantly associated with greater deficits in cognitive functions than those with primary MDD.

Clinical pharmacology of atypical antipsychotics: an update.

This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects.

Suicide attempts in schizophrenic patients: clinical variables.

INTRODUCTION: Schizophrenia is associated with a significant risk of suicide: 40-50% of schizophrenic patients report suicidal ideation at some point in their lives, and 4-13% eventually commit suicide. In order to be able to predict and prevent suicide in schizophrenic patients, it is necessary to investigate and characterise suicide victims who meet the criteria for psychotic disorders and risk factors. METHODS: The aim of this retrospective study was to verify the associations between suicide attempts (SAs) and the demographic and clinical variables of 106 patients who met the DSM-IV-TR criteria for schizophrenia. The patients were divided into two groups on the basis of the presence/absence of lifetime suicide attempts, and their main demographic and clinical characteristics were analysed and compared. RESULTS: The patients with a history of SAs frequently had a duration of untreated psychosis (DUP) of ≥1 year (chi-squared test=9.984, df=1, p=0.0016). They also showed significant associations with the presence of a depressive dimension (chi-squared test=4.439, df=1, p=0.0351), hospitalisations before SAs (chi-squared test=25.515, df=1, p <0.001), and a family history of psychiatric disorders (chi-squared test=12.668, df=2, p=0.0018) or suicidal behaviours (chi-squared test=18.241, df=2, p=0.0001). Finally, they were more frequently prescribed typical antipsychotic agents. CONCLUSIONS: The severity of psychiatric symptoms indicates a high risk of suicide in schizophrenic patients. Further prospective studies of larger samples should investigate the role of early interventions and atypical antipsychotic treatment in reducing the risk.

Safety of SSRIs during pregnancy: a controlled study.

OBJECTIVE: The objective of our study was to analyze the efficacy and the safety of SSRIs during pregnancy. METHODS: A group of 30 pregnant women affected by Major Depressive Disorder by SCID I interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision criteria) and treated with selective serotonin reuptake inhibitor (SSRI) were included in the study. They were matched to a comparison group of 26 pregnant women. RESULTS: There were no statistically significant differences in any of the pregnancy outcomes of interest between the treated women and comparison group. There was no statistically significant association in newborns of women treated with an SSRI and the control group in the first and fifth minute Apgar score, and no newborns were admitted to neonatal Intensive Care Units. CONCLUSIONS: No definitive association between use of SSRIs during pregnancy and an increased risk of birth defects or other adverse outcomes could be found.

Aggression and psychopharmacological treatments in major psychosis and personality disorders during hospitalisation.

BACKGROUND: A number of large-scale studies have shown that there is a relationship between many psychiatric disorders and aggression or violence. As no medication is currently approved for the treatment of aggression, pharmacotherapy (often involving drug combinations) is used on a trial-and-error basis with various degrees of response. METHOD: The study involved 244 in-patients aged 19-83 years (mean 41.9 ± 11.3 SD). The Modified Overt Aggression Scale (MOAS) was used to assess any aggressive or violent behaviors occurring in the week before admission and upon discharge. Psychopathology was assessed using the Brief Psychiatric Rating Scales (BPRS). RESULTS: All of the patients showed a significant improvement (p<0.001) in mean weighted total MOAS scores at the end of the study, with no significant differences between the various drugs or combination therapies. The patients who received combination treatments including antidepressants showed a worsening in the weighted total MOAS score (18.46% ± 114.31% SD); the patients who did not receive antidepressants had an improvement (13.61% ± 257.36% SD) (p=0.0069). CONCLUSIONS: Multivariate testing of the variables age, gender, substance/alcohol abuse, the duration of hospitalisation, the administration of mood stabilisers, and the use of typical or atipical antipsychotics showed that the severity of the psychopathological picture correlated significantly with the presence of violence, whereas the effect of combined antidepressant treatment on violent behavior was only relative.

Clinical outcome and tolerability of duloxetine in the treatment of major depressive disorder: a 12-week study with plasma levels.

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor that has been recently approved for the treatment of major depressive disorder (MDD). However, little is known about the relationship between DLX plasma levels and clinical response. The aims of this open-label study were 1) to assess clinical outcome and tolerability of DLX by means of clinician and patient assessments and 2) to evaluate the value of plasma DLX levels as predictors of clinical response and tolerability. This was a naturalistic, open-label study of 45 outpatients affected with MDD (16 men and 29 women), who received DLX at doses of 30-120 mg/day and were evaluated at baseline (T0) and after 2, 4 and 12 weeks (T1-3). The assessments included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA), Clinical Global Impression-Severity (CGI-S), Beck's Depression Inventory (BDI) and a mood visual analogue scale (VAS). Compared with T0, there were significant improvements in HRSD at T1, T2 and T3 (P < 0.001), in HRSA, CGI-S and the self-administered BDI at T2 and T3 (P < 0.001), and in the VAS scores shown at T3 (P = 0.01). DLX treatment was safe and well tolerated. Plasma DLX levels at T2 ranged from 5 to 135 ng/mL (mean +/- SD = 53.56 +/- 39.45) and correlated almost significantly with the DLX dose (r = 0.35; P = 0.069). There was a significant curvilinear quadratic relationship between the improvement of HRSA scores and plasma DLX levels (R(2) = 0.27; P = 0.02). The incidence of anxiety or irritability was associated with the highest plasma levels. Our findings suggest that monitoring plasma DLX levels may be helpful in predicting better treatment responses and tolerability. The present data seem to suggest an optimal anxiolytic efficacy of DLX at intermediate plasma levels.

Psychiatric diagnosis and aggression before acute hospitalisation.

OBJECTIVE: To examine the predictors of aggressive behaviours occurring before acute hospitalisation. METHODS: We analysed 350 acute admissions to a psychiatric ward during a 12-month period. The diagnoses were formulated according to the DSM IV axis I and II criteria. Aggressive behaviours occurring in the week before admission were retrospectively assessed using the modified overt aggression scale. The patients' clinical and sociodemographic variables, concurrent drug or alcohol abuse, and admission status were recorded at the time of admission. RESULTS: Aggressive and violent behaviours were highly prevalent, respectively, in 45% and 33% of the cases. Violence before admission was independently associated with drug abuse, involuntary admission status, and severe psychopathology. A diagnosis of a psychotic disorder did not increase the risk of aggression or violence, compared to the other psychiatric diagnoses. Personality disorders were significantly more associated to aggressive behaviours than psychotic disorders. CONCLUSION: The diagnosis of psychotic disorder is a poor predictor of aggression in a sample of psychiatric patients. Other clinical and non-clinical variables are associated to aggression before hospitalisation: they include drug abuse, involuntary admission status, general severity of symptoms, and diagnosis of personality disorder.

Ziprasidone outcome and tolerability: a practical clinical trial with plasma drug levels.

INTRODUCTION: The aim of this study was to evaluate clinical outcomes and the tolerability of ziprasidone in relation to its plasma levels. METHODS: Thirteen inpatients affected by schizophrenia were included in the study after an acute exacerbation phase. Ziprasidone monotherapy was administered for a period of eight weeks at a mean dose of 123.07+/-30.38 mg/day. Plasma concentrations were measured by high-performance liquid chromatography. RESULTS: Nine patients completed the study. A significant clinical improvement was observed, especially in negative symptoms ( P<0.05), and there was a significant improvement in extrapyramidal symptoms ( P<0.01). Clinical laboratory tests, such as ECG and weight, did not significantly change from baseline. Plasma ziprasidone levels ranged from 20 ng/mL to 160 ng/mL (mean: 75.8 ng/mL) and were significantly related to the improvement in negative symptoms. DISCUSSION: The study showed that ziprasidone was effective and tolerable, that use of ziprasidone was characterized by an absence of extrapyramidal symptoms and weight gain, and that no alterations in clinical laboratory tests occurred. The findings suggest a relationship between plasma levels and the clinical response to negative symptoms of schizophrenia.

Substance abuse in first-episode schizophrenic patients: a retrospective study.

Several studies suggest a high comorbidity of substance abuse and schizophrenia, associated with higher frequency of relapse, more positive symptoms and depression, cognitive impairment, poorer outcome and treatment response. A high incidence of substance abuse is also observed in first-episode patients. Among patients with substance abuse, the onset precedes the onset of psychosis of several years in most cases. All the patients with a first episode of schizophrenia, at first admission to the Psychiatric Service of Diagnosis and Treatment of Ospedale Maggiore of Milan during the years 1990 to 2004, have been included in our study.The clinical evaluation has been obtained considering the following items of Brief Psychiatric Rating Scale (BPRS): conceptual disorganization, depressed mood, hostility, hallucinations, unusual content of thought.The results showed that 34.7% of first-episode schizophrenic patients had a lifetime history of substance abuse. The age of onset of schizophrenia is significantly lower for drug abusers than for patients without any type of abuse and for alcohol abusers (p < 0.005). In multi drug abusers, cannabis resulted the most frequently used (49%), followed by alcohol (13%), and cocaine (4%). Substance abusers have obtained a significant higher score in "thought disturbance" item (p < 0.005) and in "hostility" item (p < 0.005) compared to non substance abusers. Non drug abusers showed lower mean scores of "hostility" item compared to cocaine abusers and multi drug abusers (p < 0.005). Our findings seem to indicate that substance abuse in the early course of illness determines an earlier onset of schizophrenia and increases severity of some psychotic symptoms like "hallucination" and "unusual content of thought". Therefore persons incurring a risk of schizophrenia may be warned of the possible relation between substances and psychosis and have to be counselled against the use of them.

Clinical outcome and olanzapine plasma levels in acute schizophrenia.

PURPOSE: This open label study was performed to evaluate the relationship between the plasma concentration of olanzapine and the response in acute schizophrenic inpatients. MATERIAL AND METHODS: A total of 54 inpatients, 38 males and 16 females, age ranging from 18 to 75 years, affected by Schizophrenia (DSM IV criteria) during an exacerbation phase were included in the study. Olanzapine (OLZ) was started at a dose of 5-20 mg/day and was increased to a mean dose of 15.27 mg +/-5.53 S.D. Patients were evaluated at baseline, and after 2 weeks, by using BPRS, PANNS, HRS-D, EPSE, and ACS. RESULTS: BPRS and total PANSS showed a statistically significant improvement at the end of the study. Olanzapine plasma levels (PL) ranged from 5 to 120 ng/ml (mean 33.15 ng/ml +/- 28.28 S.D.) and showed a positive correlation with OLZ dosage. A significant curvilinear correlation between OLZ PL and clinical improvement (BPRS, PANSS and HRS-D percent of amelioration) was observed. CONCLUSION: Olanzapine plasma level determination seems to be a useful tool in optimizing acute treatment particularly for more problematic cases.

Efficacy of clozapine in a non-schizophrenic patient with psychogenic polydipsia and central pontine myelinolysis.

Clozapine is an atypical antipsychotic drug that has been demonstrated to be a highly effective treatment for polydipsia in schizophrenic patients. The authors report the first case of a non-schizophrenic patient affected by polydipsia and central pontine myelinolysis who was successfully treated with clozapine.

Predictive value of amino acids in the treatment of major depression with fluvoxamine.

Sixteen outpatients (mean age +/- SD 50.18 +/- 11.55 years; 11 females and 5 males) affected by major depression without melancholia (DSM-IV) were included in the study. The control group consisted of 11 healthy volunteers (mean age +/- SD 39.90 +/- 13.39 years; 2 females and 9 males). Patients were treated with fluvoxamine (FVX) 100-300 mg daily. Clinical assessment was performed using the Hamilton Rating Scales for Anxiety and Depression (HRS-A; HRS-D) and the Clinical Global Impression Scale (CGI) at basal time (T(0)), after 4 weeks and after 8 weeks (T(8)). Plasma and platelet amino acid levels were determined at T(0) in all the subjects and also at T(8) in depressed patients. A significant clinical improvement was observed in depressed patients according to the HRS-A (p = 0.004), HRS-D (p = 0.008) and CGI (p = 0.002). A negative correlation (r = -0.53, p = 0.049) was found between platelet levels of valine and HRS-D improvement rate. Patients showed significantly higher tyrosine/large neutral amino acids (LNAAs) and lower tryptophan/LNAAs, ratios which could represent an index of good response to a serotonergic drug like FVX.

A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics.

1. The study evaluated the efficacy of amisulpride, fluoxetine and clomipramine at the beginning of the re-feeding phase of the treatment of restricting anorexia nervosa according to DSM-IV criteria. 2. 13 patients, mean weight 37.61 kg +/- 9.80 SD, were treated with clomipramine at a mean dosage of 57.69 mg +/- 25.79 SD; 10 patients, mean weight 40.90 kg +/- 6.98 SD, were treated with fluoxetine at a mean dosage of 28.00 mg +/- 10.32 SD; 12 patients, mean weight 38.41 kg +/- 8.33 SD, were treated with amisulpride at a mean dosage of 50.00 mg +/- 0.00 SD. 3. Clinical evaluation was carried out under single-blind condition at basal time and after three months by a structured clinical interview, the Eating Disorder Interview based on Long Interval Follow-up Evaluation (LIFE II BEI). 4. Patients treated with amisulpride showed a more significant increase (p=0.016) of mean weight. Concerning weight phobia, body image disturbance and amenorrhoea, no significant difference resulted.

Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels.

Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years +/- 9.96 SD were treated with risperidone (RSP) at the dosage of 2-9 mg/die (mean 4.46 mg/die +/- 1.30 SD, mean 0.06 mg/kg +/- 0.01 SD) for a year. Clinical evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1 (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy-risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method. BPRS and PANSS mean values showed a significant improvement during the study. No correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active moiety resulted. A positive correlation between age and active moiety was observed. A positive correlation between RSP and 9OH-RSP plasma levels was observed. A curvilinear relationship between active moiety and PANSS improvement (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH-RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective drug. It seems, however, difficult to devise appropriate dose schedules and plasma level determination seems to be necessary in some cases.

Gabapentin and the Prophylaxis of Bipolar Disorders in Patients Intolerant to Lithium.

OBJECTIVE: Gabapentin (GBP) is a new anticonvulsant drug that has shown efficacy in the treatment of epilepsy, several neurological disorders (pain syndromes, acquired nystagmus, Huntington's chorea, amyotrophic lateral sclerosis), and more recently in the treatment of bipolar disorders. The aim of this preliminary study was to assess the efficacy of GBP as a mood stabiliser in bipolar disorders. The adverse events of GBP were also evaluated. PATIENTS AND METHODS: 21 outpatients, 13 females and 8 males (mean age ± SD: 51.90 ± 11.51 years) affected by bipolar disorder (BD), in partial remission (DSM IV) and intolerant to lithium, were treated with GBP at a dose ranging from 300 to 2400 mg/day (mean ± SD: 1010.86 ± 268.55mg; 13.81 ± 4.21 mg/kg) for 1 year. Clinical assessments were performed with the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HRS-D), the Hamilton Rating Scale for Anxiety (HRS-A) and the Manic Rating Scale (MRS) at baseline (T0), after 15 days (T0.5), after 30 days (T1), and then every month for 12 months. RESULTS: Mean HRS-D, HRS-A and MRS scores did not show any significant variation during the study. Only one patient showed a clinical relapse. The most frequent adverse events reported by patients were dizziness (1%), dry mouth (1%) and sedation (0.5%). There was a significant negative correlation between GBP dosage (mg/kg) and HRS-A score. Mean leucocyte and neutrophil counts showed a significant increase during the study. CONCLUSIONS: These preliminary data show potential efficacy and good tolerability of GBP in the prophylaxis of BD, but double-blind studies are required.

"Postpsychotic depression" and residual schizophrenia in a mental health hospital.

Forty three patients, mean age 55.20 +/- 9.27 SD, affected by Schizophrenia Residual Type (DSM IV, RDC criteria) and treated with neuroleptic drugs for a mean of 25.42 years (+/- 4.12 SD) were included into the study. Clinical evaluation was cross-sectional assessed by BPRScale, SAPS, SANS, HRS-D, EPSE. ACS and MMSE. Seventy percent of patients presented a "postpsychotic depression" (42%, mild; 16%, moderate and 12% serious). "Postpsychotic depression" does not seem to be influenced by neuroleptics, but it seems to be a component of residual schizophrenia in patients with a long lasting permanence in a mental hospital.

Depressive symptoms and schizophrenic relapses: the effect of four neuroleptic drugs.

1. A prevalence of depressive symptomatology, ranging from 25% to 80% has been reported during the course of schizophrenia. 2. Depressive symptoms were assessed in 144 schizophrenic patients (DSM IV) during an acute exacerbation phase. 3. Depressive symptoms showed a prevalence ranging from 5.5% (severe clinical pictures) to 54.8 (mild clinical pictures). 4. The authors did not find a correlation between depressive symptoms per se and the presence of negative psychotic symptoms. Depression may be linked not so much to negative symptoms but to the psychotic state itself. 5. Depressive symptomatology concurrently occurred with schizophrenic relapses and improved together with the psychotic clinical picture, independently of the neuroleptic drug employed. Haloperidol, haloperidol decanoate and fluphenazine decanoate all showed a similar improvement of depressive symptoms. 6. L-sulpiride showed a trend to be most effective on depressive symptomatology in comparison to the other neuroleptics.

Lithium safety in the prophylaxis of bipolar disorders: a study with plasma levels.

From many decades efficacy of lithium salts, as mood stabilizers, has been largely recognized, but their tolerability, in particular during intermediate or long-term treatments is still discussed. The most frequently described side effects can affect several organs. Aim of the study was to evaluate lithium carbonate tolerability after a "brief" (1 month-4 years), "intermediate" (5-9 years) and "longterm" (10-21 years) treatment of patients affected by Bipolar Disorders (BD). 27 patients (14 males, 13 females), aged from 20 to 78 years (mean 49.03 years +/- 14.61 SD), affected by BD, type I, according to DSM IV criteria were included into the study. Our data suggest a good tolerability of lithium salts without significant differences among the three different periods of treatment.