Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)

Nature is replete with cyclic biological rhythms ranging in periodicity from much less than a day (ultradian) to months or years (infradian) [1]. For humans, however, biological rhythms that are about 24 hours in duration (circadian) are critical to healthy functioning. Among the most important of these is the sleep-wake cycle [2]. A recent review, meta-analysis, and moderator analysis of 31 polysomnographic studies (n=574) conducted between 1968 and 2014 found that patients suffering from schizophrenia spectrum disorders have significantly shorter total sleep time, longer sleep onset latency, more wake time after sleep onset, lower sleep efficiency, and decreased stage 4 sleep, slow wave sleep, and duration and latency of rapid eye movement sleep compared to healthy controls. The findings regarding delta waves and sleep spindles were inconsistent. Moderator analysis could not find any abnormalities in sleep architecture [3]. Among healthy sleep-deprived individuals subclinical psychotic experiences are increased. While data are less clear, insomnia also may increase psychotic signs and symptoms among schizophrenic patients, suggesting a possible bidirectional pathologic effect [4]. In particular, patients vulnerable to a bipolar diathesis may have their clinical stability decompensated and driven by insomnia [5]. Thus, maintenance of adequate sleep may be a critical element in the treatment of some patients with schizophrenia spectrum disorders.

Inadequate treatment contributes not only to poor quality of life but also to an increase in disease-related societal burdens. A small subset (20–30%) of the schizophrenia patient population are treatment-resistant and financially cost approximately ten-fold more than non-treatment-resistant schizophrenia patients [1]. Numerous ineffective antipsychotic trials continue to be prescribed while clozapine, which has widespread compelling efficacy data, continues to be underutilized in treatment-resistant schizophrenia. This chapter addresses clozapine efficacy in not only treatment-resistant psychosis but also comorbid suicidality and aggression, as well as treatment-resistant mania. Further, initiation and maintenance of clozapine treatment is summarized.

Typical or first-generation antipsychotic (FGA)

In community settings, the most common barriers to independent living, employment, and stable interpersonal relationships for patients suffering from schizophrenia-spectrum disorders or other psychotic disorders are negative symptoms and cognitive deficits [1]. In contrast, severely mentally ill individuals, often incarcerated or chronically institutionalized, more frequently experience substantial barriers related to positive psychotic symptoms leading to problematic behaviors such as aggression or violence [2]. This is not to say that among the chronically institutionalized severely mentally ill population that positive psychotic symptoms are the only, or even majority, source of problematic behaviors. A survey conducted within the California Department of State Hospitals, a circa 7000-bed system dedicated to the treatment of conserved and forensically committed patients, reviewed 839 episodes of aggression or violence by 88 persistently aggressive inpatients and found that 54% of such episodes were impulsive, 39% were predatory or instrumental, and 17% were psychotically driven [3]. Nevertheless, amelioration or control of positive psychotic symptoms commonly forms the initial treatment focus among the severely mentally ill [4].

Typical or first-generation antipsychotic (FGA)

Typical or first-generation antipsychotic (FGA)