Adding Suicide Prevention to the Triple Advantages of Injectable Long-Acting Second-Generation Antipsychotics

Abstract

With the advent of new treatment perspectives for schizophrenic patients, long-acting injectable antipsychotics promise to provide relapse prevention, neuroprotection, and lower mortality rates (1). In preliminary studies, scholars have also indicated that such treatments could play a central role in suicide prevention in patients (2, 3) for whom suicide is the most likely cause of premature death, in addition to repercussions for caregivers and clinicians. Both Kraepelin (4) and Bleuler (5) highlighted the issue of suicide risk among patients suffering from schizophrenia. Modern studies provided an intricate list of risk factors for suicide, pointing to numerous issues in the management and treatment of schizophrenic patients. Individuals at higher risk are generally unmarried young white males who achieved proper functioning before the onset of the disorder (6). Such patients may easily be overwhelmed by hopelessness and depression, as well as becoming demoralized and being aware that their previous lifestyle cannot be maintained. Such patients feel socially isolated, fear further mental deterioration, have higher rates of substance abuse, and may lose faith in the treatments. Suicide attempts and hospitalizations are frequent, and each time they may realize that both medical and family support is limited; moreover, ad hoc interventions are not available or are difficult to implement. There are also further risk factors for suicide in schizophrenia, such as post-psychotic depression, agitation or motor restlessness, poor adherence to treatment, and command hallucinations (although not well ascertained in terms of statistical significance). However, risk factors often yield too many false positives, pointing to the need for suicide assessments based on factors such as an understanding of mental pain and demoralization, as well as therapeutic relationships, foreseeable life events that may impact the patient, social support, and the available resources. Furthermore, suicide risk is indirectly related to relapse, illness progression, the number of hospitalizations, and plans for rehabilitation after discharge (7). Each admission to a psychiatric ward may represent a further loss of hope and faith in the treatments. The risk of suicide seems to peak not only shortly after discharge, as reported routinely in the literature, but also shortly after admission (7). This fact points to the implementation of human–environmental factors for providing ward safety and close supervision in both inpatient and community settings, especially in the cases of reduced adherence to treatment. Among the various risk factors, preventative actions should be directed over those factors that are modifiable and can be targeted by proper treatment actions (8). Furthermore, suicide risk seems to be higher when patients develop demoralization syndrome, in which repeated exacerbations of psychotic symptoms, functional deterioration compared with premorbid abilities, and a non-delusional awareness of the effects of an illness can lead to feelings of hopelessness, depression, and, ultimately, suicide. Suicidal behavior is also a major issue among patients with first-episode psychosis (9, 10). It is noteworthy that integrated compared with typical treatment proved to be effective in reducing both suicide and other causes of death; the Opus Study (9) demonstrated the effectiveness of this strategy. Such an intervention involved a) assertive community treatment (ACT); b) antipsychotic medication; c) psychoeducational family treatment; and d) social skills training. It resulted in lower mortality for any cause and lower suicide rates. Mortality in Schizophrenia and Pharmacological Treatment A recent study by Bitter et al. (11) highlighted the reduction in life expectancy among patients with schizophrenia. Of note is the fact that, compared with the controls, 20-year-old males with schizophrenia had their life expectancy reduced by 11.5 years and females by 13.7 years; the analogous numbers for 45-year-old schizophrenics were 8.1 and 9.6 years, respectively. Taipale et al. (12) explored mortality in a large sample of approximately 30,000 patients and found that second-generation long-acting antipsychotic therapies [SG LATs; ranking: paliperidone palmitate > oral aripiprazole > long-acting injection (LAI) risperidone > LAI haloperidol > LAI perphenazine > oral perphenazine > LAI olanzapine > LAI zuclopenthixol] were associated with the lowest cumulative mortality rate. In 7.5 years, a follow-up SG LAT observation revealed the lowest cumulative mortality rate as compared with first-generation (FG) and SG oral and with no antipsychotic use. The use of LATs reduces the risk of death by 33% when compared to the corresponding oral equivalent. Such results are in line with further investigations by the same group of researchers (13), who reported their observations over 8 years. They observed that the risk of treatment failure or relapse after discontinuing antipsychotics does not decrease over time and that patients maintaining long-term antipsychotic treatment had increased survival rates.