Activation Induced by High-Dose Ziprasidone

Evidence review and clinical guidance for the use of ziprasidone in Canada

“…From the group’s clinical experience and review of the literature, it was noted that manifestations of agitation are not well described and could be classified as illness symptoms (e.g., hypomania) or referred to as a different adverse effect (e.g., akathisia). Differences in terminology are also plausible with some references to activation [85], which may have considerable symptom overlap with manic or hypomanic symptoms, akathisia, and agitation. Patients with agitation can demonstrate a variety of behaviours (e.g., pressured or loud speech, pacing, tapping fingers or feet, starting, moaning, appearing distracted by an internal stimulus) and also manifest physiologic changes related to autonomic tone (e.g., blood pressure) and the musculoskeletal system (e.g., muscle tension) [86].…”

“…Clinical experience within the group supported that agitation at lower doses is a phenomenon reported clinically by patients and suggestions were made regarding dose initiation and up-titration, as discussed later, to enhance the likelihood of adherence in early stages of treatment. Exemplifying the challenge of ziprasidone-related agitation, Kaushik (2009) [85] reported activation with higher, not lower, doses of ziprasidone, and reviews the related literature and putative mechanisms [15]. Clinicians should also be aware of reports of mania like symptoms associated with the use of ziprasidone when considering symptoms of activation and agitation [87].…”

Ziprasidone as Adjunctive Therapy in Severe Bipolar Patients Treated with Clozapine

“…Kaushik et al [ 66 ] described the case of a patient aged 43 with schizoaffective disorder who had showed psychomotor activation after the prescription of high dose ziprasidone treatment. After nine days of ziprasidone monotherapy (at a dose of 320 mg/day), the authors reported the appearance of psychomotor restlessness, irritability, anxiety, and akathisia [ 66 ].…”

“…Kaushik et al [ 66 ] described the case of a patient aged 43 with schizoaffective disorder who had showed psychomotor activation after the prescription of high dose ziprasidone treatment. After nine days of ziprasidone monotherapy (at a dose of 320 mg/day), the authors reported the appearance of psychomotor restlessness, irritability, anxiety, and akathisia [ 66 ]. According to the data available in the literature and based on what we observed in our sample, as well as in relation to the pharmacodynamics of ziprasidone, it could be argued that lower doses are associated with more anxiolytic properties and fewer extrapyramidal side effects while higher doses may be associated with akathisia and the loss of anxiolytic effects.…”

Efficacy and safety of high-dose antipsychotic therapy

“…37 A case report described improvement in positive symptoms of schizoaffective disorder with ziprasidone, 320 mg/d, but activation, hostility, and depression worsened. 39 Compared with other antipsychotics, high-dose clozapine and quetiapine may be less likely to cause EPS due to lower D2 receptor occupancies. 40 Nevertheless, increased activity at other postsynaptic receptors may lead to constipation, metabolic effects, and sedation.…”