Clozapine is still the drug of choice for patients with schizophrenia. However, there are still many patients not having a satisfied response to clozapine. In these patients clozapine is very often combined with other antipsychotics but the evidence for these combinations is poor. Due to the receptor profile of clozapine, the augmentation drug should be a non-sedating drug with no muscarinergic affinity and still have a low propensity to cause EPS. Sertindole has not been investigated as an augmentation drug to clozapine.

We present a 29 year old man with a treatment resistant schizophrenia. Currently he was treated with 400 mg of clozapine with a suboptimal response but was not able to tolerate a higher clozapine dose due to sedation. Sertindole 16 mg was instead added.

The baseline PANSS total score was 123 and after 12 weeks it was reduced to 90. No subjective or objective side-effects were seen.

Sertindole might be an ideal augmentation drug to clozapine due to the receptor profile but whether the combination is beneficial needs to be determined in a randomized double-blinded placebo trial.

Antipsychotic medications are used for the treatment of schizophrenia and other psychotic disorders. The aim of our study was to assess the off-label use of atypical antipsychotics (AA) in the Crisis Intervention Unit (CIU), Ljubljana, Slovenia.

Hospital records of 105 consecutive patients that were admitted to the CIU in the period of 4 months (June – September 2007) were included to the retrospective observational study. Patients were screened for diagnosis (ICD-10), gender, age, suicidal behavior and for prescribed psychotropic medications. Off-label use of atypical antipsychotics for diagnoses other than psychosis was evaluated. We noted which specific antipsychotics were prescribed for specific diagnoses with their daily dosages transformed to chlorpromazine units (CPU).

Most patients suffered for stress related disorders (48%), depression (32%), anxiety disorders (14%) and other disorders (6%). Gender ratio was in favour of women (77%). Average age of patients was 52,1 years. 27% of patients were admitted after the suicide attempt, 46% reported suicidal thoughts. Off-label use of AA was noted in 65% of patients who suffered from stress related disorders, in 36% of patients with depression and in 49% of patients with anxiety disorders.

Our results show that atypical antipsychotics are widely used for indications other than psychosis, even though the long-term effects of their use are not yet known and safety issues remain to be examined further.

To compare the relative effectiveness and tolerability profile, in terms of Number Needed to Treat (NNT) for all causes of medication discontinuation and Number Needed to Harm (NNH) for 7% of increased of body weight of olanzapine, risperidone, typical (oral and depot) and other atypical antipsychotic medications (quetiapine and amisulpride) in previously untreated outpatients with schizophrenia during 36-month follow-up.

NNTs (NNHs) mean the number of patients needed to be treated with one antipsychotic instead of another to prevent (produce) one negative outcome.

Previously untreated patients with schizophrenia were defined as patients who i) had never received antipsychotic treatment for schizophrenia and ii) had not received antipsychotic treatment in the 6 months prior to study inclusion. Rate of medication discontinuation for any cause during the 36 months post initiation was calculated for olanzapine (28.9%), risperidone (36.2%), typicals (44.5%) and other aypicals) (34.7%). Cox and logistic regression models were employed to adjust for treatment group differences at baseline and NNTs and NNHs with their 95% confidence intervals were calculated.

The NNTs for all-cause discontinuation of olanzapine were: 12.2.(95% CI: 5.8; 229.7) for olanzapine vs. risperidone, and 6.2 (3.1 ; 37.8) for olanzapine vs. typicals. The NNH for 7% weight gain was -3.7 (-2.6 ; -9.5) for olanzapine vs. typicals.

Treatment effectiveness and tolerability varied among medications. The NNTs for olanzapine therapy were consistently better when compared to other treatment cohorts. The weight-gain NNHs for olanzapine treatment were less favourable when compared to other antipsychotic medications.

Drug Attitude Inventory1 (DAI-30) is a valid and reliable tool, recently and largely used in clinical trials to investigate the patients’ opinion towards therapy2. The questionnaire, covering two different constructs, attitude towards medication (AM) and subjective response (SR) has been used to get a valid measurement of attitude towards RLAI.

DAI-30 was administered to 347 subjects with schizophrenia or schizoaffective disorder treated for 52 weeks with RLAI, at baseline and at any protocol visit (month 1 and every 3 months). Clinical assessment by Positive and Negative Syndrome Scale (PANSS) and Global Assessment Scale (GAF) was also performed.

The DAI-30 total score significantly improved from 3rd month after RLAI therapy, with a trend towards improvement for both the constructs (AM and SR). Delta DAI-30 (52nd week – baseline total score) significantly correlated either with Delta PANSS positive scores and Delta GAF score (Pearson r 0.28 and 0.35 respectively, p<0.01). In a regression model, Delta DAI-30 is a predictive factor for the remission (17% of the explained variance, p<0.001) according to the Andreasen et al. criteria3.

A one year treatment with RLAI shows symptom and global functioning improvements with a positive attitude for the established and accepted antipsychotic therapy influencing the remission.

Actual treatment outcomes are directed towards preventing relapses, instead of new perspective of functional recovery feasible with the achievement of a prolonged remission which is defined, according to Andreasen1, in severity criteria: PANSS items (P1, P2, P3, G5, G9, N1, N4, N6) scores <3 and duration criteria (maintenance of score for at least 26 weeks) here applied to 243 subjects with schizophrenia or schizoaffective disorder treated for 1 year with RLAI.

Although subjects were stable, only 14% of them met the PANSS severity criterion for remission at baseline with an increase to 45% after 1 year. 63% of subjects who were in remission at baseline maintained the criterion at the end of the study, while the 26% of subjects not in remission at baseline reached the criterion after 1 year. In addition, 32% of subjects met both severity and duration criteria for remission at 12 months. The decrease in PANSS total score from baseline (88.4+22.0) to 12 months (69.6+22.9; p<0.001) is associated to the remission (Chi Square test, p<0.001). At baseline, the difference in CGI-S and GAF scores between remitted subjects and non remitted is significant (p<0.001). In remitted subjects, the improvement in PANSS cognitive factor is higher (p<0.001) than that observed in non remitted subjects.

This study shows that RLAI treatment up to 1 year warrants efficacy maintenance with a significant and sustained symptom improvement, enabling the subjects to achieve and maintain the remission criteria for schizophrenia.

Long term antipsychotic therapy is recognized as being important for preventing relapses and improving outcomes in patients with schizophrenia. In this respect the treatment with RLAI has been shown to be effective and well tolerated in long-term studies lasting up to 12 months1-2.

A 52 weeks open label trial has been performed in 347 stable subjects with schizophrenia or schizoaffective disorders, switching from any previous antipsychotic treatment, in order to evaluate the maintenance of efficacy of RLAI.

70% of subjects completed the study. Mean PANSS total score significantly improved at each assessment visit 4, 12, 26, 38 and 52 weeks (p<0.001). Similar improvements were observed for the PANSS positive, negative and general psychopathology subscales. At 52 weeks, 58% of patients had a > 20% improvement in the PANSS total score compared to baseline. Functionality as measured by GAF improved at each assessment visit till week 52 (p<0.001). Significant improvement was also seen for CGI evaluation (p<0.05). Treatment with RLAI was well tolerated: 30% of subjects experienced at least 1 adverse effect (AE), and 52% of the AEs were mild and 81% did not require treatment change. Only 3% subjects experienced an extrapyramidal symptom related to RLAI. No significant (p=0.09) weight gain was observed.

Direct transition to RLAI in psychotic subjects offers a better, significant and sustained control of symptoms with a good tolerability profile.

Of all the Second-Generation Antipsychotics (SGAs) risperidone and amisulpride have the highest propensity to elevate prolactin levels. Ziprasidone seems to be less frequently associated with hyperprolactinemia and aripiprazole may even lower prolactin levels. We describe the case of a patient who developed clinically significant hyperprolactinemia while taking both amisulpride and ziprasidone, which resolved with the introduction of aripiprazole

Ms. A a 22- year old woman had a history of paranoid schizophrenia. Two years ago, she was treated with amisulpride 400 mg/day. After 8 weeks of amisulpride treatment, the patient complained of galactorrhea and amenorrhea and her prolactin level was 54 ng/ml. Brain magnetic resonance imaging showed no evidence of a pituitary microadenoma. Two weeks after she stopped taking amisulpride, her prolactin level was 3.8 ng/ml and she menstruated 1 week later. She was given ziprasidone 120 mg/day. Her psychotic symptoms disappeared, but she did not menstruate and her prolactin level rose to 37,4 ng/ml. Ms. A was switched to aripiprazole 10 mg/day.

Only 2 days after the beginning of aripiprazole treatment, the patients prolactin level decreased to 5,6 ng/ml. Her menses resumed with 3 weeks of stopping ziprasidone and remained regular for at least 20 months. Her prolactin level remained normal (the last one was 3,23 ng/ml).

While aripiprazole appears to modulate dopaminergic and serotonergic neurotransmission in a manner similar to that of SGAs, it's partial D2 receptor agonism provides decreased liability for hyperprolactinemia.

Aripiprazole and quetiapine are the two most recent second generation antipsychotics available in the UK. We aimed to study patients who were prescribed aripiprazole and quetiapine in routine clinical practice, to identify and compare patients who had a good clinical response.

From a data set of 22,000 electronic patient records (from 2002 to 2007), we retrospectively identified all secondary care psychiatric patients started on aripiprazole and quetiapine for schizophrenia and other psychotic disorders. We retrospectively assigned a severity and an improvement score of Clinical Global Impression (CGI) to records, to measure the effectiveness of both drugs.

89 patients were newly prescribed aripiprazole and 132 patients prescribed quetiapine, for schizophrenia and other psychotic conditions. Patients on aripiprazole had a lower initial severity of illness, CGI (Severity) 3.9 versus 4.4, p=0.0003. After excluding treatment resistant patients, a CGI (Improvement) score 1-4 (minimally to very much improved) was achieved with aripiprazole in 69% and quetiapine in 71% of patients. There were no statistical differences in overall discontinuation rates (aripiprazole 40%, quetiapine 41.5%). There were differences in mean time to discontinuation, aripiprazole,165 days, quetiapine, 267 days (p=0.017)

This study is an independent comparison of aripiprazole and quetiapine in schizophrenia and psychoses. Both aripiprazole and quetiapine were clinically effective in the majority of patients. CGI improvement scores were similar for both drugs as were overall discontinuation rates. Patients on aripiprazole, however, discontinued earlier than those discontinuing from quetiapine.

Atypical antipsychotic use in youth has increased. Adverse metabolic effects on weight, lipids, and glucose are evident in adults, but inadequately studied in youth. This report focuses on the metabolic effects of these agents in psychiatrically hospitalized youth.

Inpatient subjects were assessed at admission, 3 weeks, and discharge. Weight, body mass index, blood pressure, fasting glucose levels, high and low density lipoproteins (HDL and LDL, respectively), and triglycerides were measured.

N=112 subjects, diagnosed as: Affective Disorders (26.4%), Disruptive Behavior Disorders (32.6%), Pervasive Development Disorders (9.3%), Psychotic Disorders (5.4%), and Others (26.3%). Ages ranged from 4-17 years. Patients received: risperidone (N=41), olanzapine (N=13), quetiapine (N= 15), aripiprazole (N=22), while 34 patients received no medication. Average length of hospital stay (LOS) was 55.9 days (1-289). For the sample as a whole, trends of statistical differences were noted in weight at the time of discharge (+3.79 lbs). Weight gain at discharge was significantly correlated with only olanzapine (r=.553, p<0.0001), multiple regression analysis controlling for LOS is also significant (Beta .558, p < 0.0001) for olanzapine. For the medication treated group, statistically significant increases in HDL are noted at three weeks (+ 5 mgs/dl, p = 0.023); at discharge the difference was not significant. A similar trend was observed for glucose. There was a statistical trend for decrease in triglycerides at 3 weeks (15 mg/dl, p = 0.054), discharge difference was non-significant (-9 mg/dl).

Certain agents may carry greater propensity for inducing certain metabolic changes, but further study is required.

To compare the efficacy and tolerability of first- and second-generation antipsychotics (FGAs & SGAs, respectively) in the treatment of psychotic disorders.

PANSS scale was employed to measure disease severity and the efficacy of treatment. In all participants PANSS score was calculated on admission, before releasing the patient, and in case of any change in antipsychotic treatment schedule. Demographic data and comprehensive information on psychotropic medication status were collected for all patients.

377 patients (51,5% males) admitted to the Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, have been recruited for the study. Eighty two percent of participants were suffering from schizophrenia. The average improvement in PANSS score amounted to 22,85%. The demographic and clinical characteristics of patients being prescribed FGA or SGA were comparable. No statistically significant differences in the efficacy of FGAs vs SGAs, as well as mono- vs polytherapy were observed. SGAs were better tolerated than FGAs. A higher initial severity of symptoms was the only predictor of a major, over 40% improvement in PANSS score. FGA and SGA therapies proved equally effective in generating such substantial decreases in symptoms’ severity.

In our sample, the efficacy of FGAs and SGAs in the treatment of psychotic disorders was comparable. The tolerance of SGA therapy was better than for FGAs. Therapeutic success seems to be more dependent on adequate dosage than the class of an antipsychotic agent.

Olanzapine and aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia. Hyperprolactinaemia is a frequent side-effect in the use of atypical antipsychotics. The endocrine and sexual side effects related to hyperprolactinaemia significantly impair in breast cancer patients.

The effect combination of a low doses olanzapine and aripiprazole were examined in a sample of 21 breast cancer patients who had the schizophrenia and olanzapine-induced hyperprolactinaemia. They were randomly assigned to experimental or control groups. They were interviewed by psychiatrists and tested using Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up visits. Plasma prolactin level was assessed at baseline and at the end of the study. The patients of control group received olanzapine as their sole antipsychotic agent at a maximum dose of 5 mg once daily. The patients’ experimental group received olanzapine at a maximum dose of 5 mg once daily in combination with aripiprazole at a maximum dose of 10 mg once daily.

No differences between initial groups were identified. The results of our study suggest that after three weeks of schizophrenia treatment, 81,8% patients from the experimental group and 40% from the control group showed significant clinical improvement. At the end of weeks 3, serum prolactin levels were normalized (7.9+/-4.7 micrograms/L) in patients’ experimental group.

These data show that combination of a low doses olanzapine and aripiprazole for treatment schizophrenia in breast cancer patients may result in enhanced antipsychotic efficacy while reducing adverse effects including olanzapine-induced hyperprolactinaemia.

Subjective experience on antipsychotic drugs (APs) in schizophrenic patients has been the object of several recent studies and it has been connected to treatment adherence, quality of life and outcome. The current study was undertaken to investigate the role of clinical and socio-demographic variables on patients' perceptions and attitude towards APs in schizophrenia.

Seventy-eight schizophrenic patients (M/F=38/35) were recruited in a naturalistic setting, from two Rehabilitative Centres of the Departments of Mental Health of Melegnano and Milano (Italy). Subjective experience towards antipsychotic treatment was assessed using the Drug Attitude Inventory-30 (DAI-30) and the Subjective Well-being on Neuroleptics (SWN) scales. The Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Global Assessment of Functioning (GAF) scale were adopted to evaluate clinical and outcome variables.

The analysis of study data showed a relationship between psychopathological variables and patients’ subjective experience on APs treatment. Positive symptoms affected patients’ perception of their treatment leading to a negative attitude towards APs, whereas negative symptoms were associated with a worse perception of patients’ mental functioning. With respect to pharmacotherapy, atypical antipsycotics were associated to a higher awareness of cognitive dysfunction and better treatment adherence.

These findings underline the clinical relevance of taking into account the subjective experience of schizophrenic patients treated with APs in order to improve treatment adherence and outcome.

Recently, the SOHO, CATIE and CUTLASS studies showed that molecules which apparently showed the most side effects are not only the most effective but also tend to cause to the least frequent changes in treatment. Can we generalise this assertion ?

Review of the literature addressing comparing efficiency of treatments and cost efficacy studies. Result: Although we witness a profusion of publications about the efficiency of given molecules vs placebo, studies comparing molecules are scarce, and studies on cost efficacy in natural environments are even scarcer. The last few years’ efforts to completely minimise side effects seem to have resulted in a reduction of medication efficacy. Moreover, the previously held hypothesis suggesting that the fewer the side effects, the less the need to change treatment has been proven wrong. The duration of a treatment is more dependent upon its efficiency.

Clinicians cannot use the absence of noxiousness of a molecule as their primary criterion of choice. They should carefully balance side effects and efficiency. There is a lack of studies about cost-efficacy and, in the interpretation of such studies it is essential that the limitations of the studies be taken into account, and their results should not be over-generalised. There is a danger that such misinterpretation of results may lead us to abandon the use of some of our most effective molecules, even though the data actually favours the use of Effective drugs with the appropriate monitoring of and dealing with side effects.