Ziprasidone is an atypical antipsychotic that has demonstrated efficacy for the treatment of bipolar disorder and schizophrenia. There is some preliminary evidence for Ziprasidone use in children and adolescents with several open label studies and some randomized control trials, therefore it is advantageous to understand where Ziprasidone lies in the treatment algorithm of children and adolescents.

The aim of our study is to examine the efficacy and tolerability of Ziprasidone in children and adolescents.

We conducted a literature search consisting of open label or randomized control trials (RCT) that report on Ziprasidone use in children on the PubMed database. We found 13 studies (11 open label and 2 RCT) that met our inclusion criteria. Our outcome measures included efficacy measures such as BPRS, YMRS, CGI-S and adverse effects such as weight gain, increase in BMI, QTc prolongation, sedation, dizziness and EPS.

Data from thirteen studies was meta-analyzed (Total n= 560, mean age=13.16 years, male= 70.35% that reported the use of Ziprasidone in children and adolescents. We found that Ziprasidone was efficacious in children and adolescents in measures of BPRS (-13.493, p<0.05), YMRS (-14.225, p<0.05), CGI-S (-1.430, p<0.05). In measures of adverse effects, Ziprasidone was not found to cause any significant weight gain (0.164, p>0.05) or change in BMI (-0.159, p>0.05). QTc prolongation was found to be significant (13.122, p<0.05).

Ziprasidone is an efficacious in children and adolescent population. It does not cause significant weight gain, however QTc prolongation and sedation were found to be the most significant side effects .

No significant relationships.

Studies have demonstrated that Ziprasidone use may be beneficial in children. Determining its potential risks and benefits when used in children is therefore important.

To examine the tolerability of Ziprasidone, an atypical antipsychotic, in children and adolescents.

We conducted a literature search of open label or randomized control trials that report on Ziprasidone use in children on three databases: Embase, PsychInfo and PubMed using the PRISMA guidelines of Systematic review and Meta-analysis. Out of 1690 articles, 11 studies met inclusion criteria. Outcome measures included adverse effects such as weight gain, increase in BMI, QTc prolongation, changes in metabolic parameters, sedation, and dizziness. We conducted a random effects meta-analysis and meta-regression of potential moderators. Publication bias was assessed with funnel plots.

Data from Eleven studies was meta-analyzed (Total n= 474, mean age=12.87 years, male= 68..37%) that reported the use of Ziprasidone in children and adolescents with Psychosis, Bipolar, Autism spectrum disorders and Tourettes syndrome. Mean Ziprasidone dose = 84.40 mg and mean study duration = 2.85 months). We found that Ziprasidone was not found to cause any significant weight gain (1.72, p>0.05) or change in BMI (0.58 , p>0.05). QTc prolongation was found to be significant (11.9 , p<0.05). Most common side effects were sedation (42.44%), Nausea(19.32%), Headache (22.92%), fatigue (16.67%) and Dizziness (16.96 %).

Results demonstrate that Ziprasidone does not cause significant weight gain, however QTc prolongation and sedation were found to be significant side effects of Ziprasidone use. Therefore, baseline EKG and thorough history must be obtained before prescribing Ziprasidone in children and adolescents.

No significant relationships.

To characterise patients with schizophrenia from four European countries treated with ziprasidone, and to compare these with patients treated with other second generation antipsychotics (SGAs) included in this survey.

A randomly selected, representative sample of psychiatrists (N = 744), from Germany, Greece, Italy and Spain, collected data on the five last patients with schizophrenia they had seen in consultation (N = 3996), including up to two patients treated with ziprasidone (N = 1096).

Ziprasidone was most frequently prescribed to patients requiring a switch from another antipsychotic. Compared to other surveyed SGAs, ziprasisone was more likely to be prescribed to women than to men (OR: 1.52), to patients with mild disease than to those with severe disease (OR: 1.94) and to outpatients than to inpatients (1.30). The most frequently cited reasons for prescribing ziprasidone were good tolerability and efficacy against positive and negative symptoms. Compared to other SGAs included in this survey, it was more likely to be prescribed due to the low risk of weight gain, metabolic syndrome and extrapyramidal symptoms.

Patients treated by ziprasidone more frequently belong to subgroups composed of more autonomous patients and those with mild to moderate disease severity.

The ZEISIG study (Ziprasidone Experience in Schizophrenia in Germany/Austria) investigated the effectiveness of ziprasidone as measured by discontinuation rates and mean changes of the BPRS total. Secondary objectives included quality of life, subjective well-being, tolerability, and safety.

Two hundred and seventy-six subjects with schizophrenia and schizoaffective disorder were treated within an open-label, 12-week, prospective, flexible-dose observational trial of ziprasidone (40–160 mg/day). Baseline and outcome assessments mainly included Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions Scale (CGI), Short-Form 12 (SF-12), and Subjective Well-being under Neuroleptic treatment (SWN-K).

Study discontinuation due to any cause was evident in 58% of subjects, most of them within the first 4 weeks after study initiation. In study completers, ziprasidone was associated with improvements in BPRS total (44.8 to 33.6; p < 0.001), CGI, SF-12, and SWN-K total scores (80.5 to 89.5). Ziprasidone was related to reduction of weight, fasting glucose, and serum lipids. No cardiovascular adverse event or significant increase of the QTc interval was observed.

Approximately 60% of subjects discontinued ziprasidone prematurely, probably related to an initial and overall underdose. The present study confirmed previous tolerability and safety data of ziprasidone as well as results of its effectiveness. Independent from reason to switch, previous antipsychotic class, and severity of illness at baseline, the recommended starting dose of 80 mg/day as well as the maximum treatment dose of 160 mg/day may not be sufficient for a selected subgroup of patients.

Atypical antipsychotics are increasingly used in the treatment of diverse psychiatric disorders; however, there is little information on the ‘why, when, and how’ of switching between the different atypical antipsychotics currently available.

To review the data on switching and atypical antipsychotics.

A literature search was initially conducted using the key words followed by a search of relevant articles including conference abstracts; relevant pharmaceutical companies were also contacted.

Clinical trial data are limited in terms of parameters measured, and case reports describe specific problems. Few studies are based on real world populations of psychiatric patients over the long-term. Careful patient and drug selections matched to a carefully supervised and appropriate cross titration based upon the pharmacodynamic and pharmacokinetic properties of all of the drugs involved is important to avoid potential complications such as re-emergence or worsening of psychosis and withdrawal, rebound, and emergent phenomena including new or uncovered side-effects. Psychoeducation and involvement of patients and caregivers in the process are also necessary for a successful switch.

Despite the prevalence of switching in real world clinical practice, there is a paucity of data to guide clinicians with respect to effective and safe strategies. There are no criteria defining a successful switch. With the increasing range and formulations of atypical antipsychotics available, there is a rationale for their early use to avoid the practical problems associated with switching from conventional antipsychotics as well as the opportunity to maintain patients on an optimal atypical antipsychotic monotherapy.