Suicide in schizophrenia

Meltzer, H.Y., Alphs, L., Green, A.I., et al. Clozapine treatment for suicidality in schizophrenia International Suicide Prevention Trial flhterSePT). Arch. Gen. Psychiatry 60(1), 82-91, 2003. 

Rusch N, Spoletini I, Wilke M, Martinotti G, Bria P, et al. 2008. Inferior frontal white matter volume and suicidality in schizophrenia Psychiatry Res Neuroimaging 164 206-214. 

By far, the most important contributor to suicide is a serious psychiatric disorder, with MOD, bipolar disorder, schizophrenia, and substance abuse being most closely associated with suicide. The male-to-female ratio is less pronounced among psychiatric patients than in the general population, with a higher rate in unmarried psychiatric patients living alone. The lifetime probability of death by suicide in various psychiatric disorders is estimated to be between 10% and 15%, contrasting with less than a 1 % lifetime probability in those without a psychiatric disorder. 

Older persons account for one-third of all suicides in the United States even though this group represents only 12% of the population ( 36). Suicide is even more often related to major depression in the elderly than in younger individuals in whom other causes such as substance abuse, bipolar disorder, schizophrenia, and personality disorders often play a major role. In fact, suicide rates are highest in older white men relative to any other segment of the population. For example, white men older than 85 years age commit suicide 30 times as frequently as black women. 

In view of the risk/benefit ratio for clozapine, this agent is not generally considered a first-line agent for the treatment of psychosis but one to consider when several other agents have failed. It is especially useful in quelling violence and aggression in difficult patients, may reduce suicide rates in schizophrenia, and may reduce tardive dyskinesia severity, especially over long treatment intervals. 

Mood symptoms of depression are associated with many conditions in addition to major depressive disorder, including mood and anxiety symptoms in schizophrenia, schizoaffective disorder, bipolar manic/depressed/mixed/rapid cycling states, organic mood disorders, psychotic depression, childhood and adolescent mood disorders, treatment-resistant mood disorders, and many more (see Chapter 10, Fig. 10-6). Atypical antipsychotics are enjoying expanded use for the treatment of symptoms of depression and anxiety in schizophrenia that are troublesome but not severe enough to reach the diagnostic threshold for a major depressive episode or anxiety disorder in these cases the antipsychotics are used not only to reduce such symptoms but hopefully also to reduce suicide rates, which are so high in schizophrenia (Fig. 11 — 53). Atypical antipsychotics may also be useful adjunctive treatments to anti-... 

Clozapine has been found effective in patients who did not improve during treatment with first-generation antipsychotics, and since the hematological side effects permit only its restricted use, this dmg has a unique indication for treatment- resistanf schizophrenia. Another unique indication for clozapine is the reduction in the risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorders. The indications of clozapine and its two analogues, olanzapine and quetiapine, are summarized in Tab. 13.5. The US labels of these drugs served as the data source [62-64]. Clozapine and olanzapine, but not quetiapine, are available in intramuscular form, which is helpful in the treatment of acutely agitated patients with diagnoses as defined in Tab. 13.5. 

Risk of recurrent suicidal behavior in schizophrenia or schizoaffective disorder Schizophrenia X X X... 

Hogan, T. P., Awad, A. G. (1983). Pharmacotherapy and suicide risk in schizophrenia. Canadian Journal of Psychiatry, 28, 277-281. 

Coccaro EF, Siever LJ, Klar HM, Maurer G, Cochrane K, et al. 1989. Serotonergic studies in patients with affective and personality disorders Correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry 46 587-599. Cohen JD, Barch DM, Carter C, Servan-Schreiber D. 1999a. Context-processing deficits in schizophrenia Converging evidence from three theoretically motivated cognitive tasks. JAbnorm Psychol 108 120-133. 

Reinstein MJ, Chasonov MA, Colombo KD, Jones LE, Sonnenberg JG. Reduction of suicidality in patients with schizophrenia receiving clozapine. Clin Drug Invest 2002 22 341-6. 

Wagstaff A, Perry C. Clozapine in prevention of suicide in patients with schizophrenia or schizoaffective disorder. CNS Drugs 2003 17 273-80... 

Duggan A, Warner J, Knapp M, Kerwin R. Modeling flie impact of clozapine on suicide in patients with treatment-resistant schizophrenia. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

There are data to confirm and reject the association of the Cys23Ser S-HT and the Gly22Ser 5-HTj receptor variants, characterized in vitro by reduced agonist potency, with phenotypes such as intractable suicidal ideation (98), ADHD (100), alcohol dependence, and schizophrenia (98,99,109-116). While the -1348 A/G polymorphism of the S-HT receptor has been associated with the negative symptoms of schizophrenia, other studies of eating disorders appear to be equivocal. A body of evidence is available, however, that S-HT variants may be associated with psychotic symptoms in Alzheimer s patients (94,100,117,118). 

There are two general classes of clinical characteristics of schizophrenia. First, there are the positive symptoms that include auditory hallucinations (voices) and delusions, often paranoid. Second, there are the negative symptoms these include disorganization, loss of will, inability to pay attention, social withdrawal, and flattening of affect. The relative roles of positive and negative symptoms for a particular victim vary over time. The positive symptoms may predominate for a period to be followed by one in which the negative symptoms are more prominent. About 10% of people with schizophrenia commit suicide. 

Other Symptoms. Although they are not reflected in the DSM-IV criteria, it now appears that mood and cognitive symptoms also hinder the patient with schizophrenia. Depressed mood, often short of the duration or severity needed to diagnose major depression or schizoaffective disorder, is an all too common problem. Because the negative symptoms of the illness and certain antipsychotic side effects resemble depression, this was long overlooked. Indeed, depressed mood may in part explain the extremely high rates of attempted and successful suicides by those with schizophrenia. 

The goals of treatment during the acute phase of illness are to reduce the positive symptoms of schizophrenia and to plan for extended treatment during the maintenance phase. Reducing the positive symptoms quickly is important for at least two reasons. First, the erratic behavior of an acutely psychotic patient can take a tremendous toll, risking arrest, loss of job, suicide, and the alienation of friends and family. Second, there is some evidence that psychosis itself is harmful to the brain. In other words, it may be that the longer the patient is actively psychotic, the worse the prognosis becomes. 

Recurrent suicidal behavior (except orally disintegrating tablets) - For reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for reexperiencing suicidal behavior, based on history and recent clinical state. Continue clozapine treatment to reduce the risk of suicidal behavior for at least 2 years. 

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