Suicidality with major depressive disorder

Suicidaiity in chiidren and adoiescents Antidepressants increased the risk of suicidal thinking and behavior (suicidaiity) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone... 

Suicidality in children and adolescents Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of trazodone or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Trazodone not approved for use in pediatric patients (see Clinical worsening and suicide risk and Children sections in Warnings). 

Suicide risk Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. 

Major depressive disorder (MDD) is a familial recurrent illness associated with poor psychosocial and academic outcome an increased risk for other psychiatric disorders, suicide, and suicide attempts and a high rate of depression and psychological difficulties in adult life (Birmaher et ah, 1996b Goodyer et ah, 1997 Lewin-sohn et ah, 1999 Pine et ah, 1998 Rao et ah, 1999 Weissman et ah, 1999a,b). The prevalence of MDD in children and adolescents is approximately 2% and 6%, respectively (Birmaher et ah, 1996b). Thus, early identification and prompt treatment of this disorder at its early stages is critical. 

High levels of aggression have been reported in adolescents with major depressive disorder (MDD) (Knox et al., 2000). Delinquent youth and youth with CD have high rates of affective illness (Puig-Antich 1987 Pliszka et al., 2000). Children and adolescents suffering from both MDD and antisocial behavior are at highest risk for suicidal acts (Brent et al., 1993). 

The clinical implications of such data point to a relationship between abnormalities in the central serotonin system and self-injurious behavior. These findings have led to an interest in developing specific drugs that alter 5-HT activity to treat suicidality, impulsivity, and aggressivity independent of any specific psychiatric disorder. Central serotonin function can be enhanced by agents such as lithium and various serotonin reuptake inhibitors. Recent studies have found that the use of such agents is associated with reductions in the likelihood of suicide attempts and completions in both patients with major depression and those with cluster... 

BZDs may exacerbate depression and possibly increase suicide risk. Case reports and clinical trials also indicate that BZD treatment of generalized anxiety and panic may result in emergence of depression (215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225 and 226). In some of these reports, depression is ill-defined, but in others, it met DSM-III criteria for a major depressive disorder, requiring treatment with an antidepressant ( 225, 226). Depression has been reported with a variety of BZDs (alprazolam, bromazepam, clonazepam, diazepam, lorazepam), but there is no evidence that one is more likely than another to cause or aggravate depressive illness. 

A serious complication of PD is the abuse of sedatives and alcohol through attempts at self-medication. In several studies, those who did well on antidepressants did not return to alcohol or drug abuse, but those in the control groups, not maintained on medication, often returned to a level of drug abuse that eventually necessitated rehospitalization. Another complication is the risk of suicide, which may be as high in patients with PD as in those suffering from a major depressive disorder (3, 4, 5 and 6). 

The diagnosis of depression still rests primarily on the clinical interview. Major depressive disorder (MDD) is characterized by depressed mood most of the time for at least 2 weeks and/or loss of interest or pleasure in most activities. In addition, depression is characterized by disturbances in sleep and appetite as well as deficits in cognition and energy. Thoughts of guilt, worthlessness, and suicide are common. Coronary artery disease, diabetes, and stroke appear to be more common in depressed patients, and depression may considerably worsen the prognosis for patients with a variety of comorbid medical conditions. 

Estimates associate 16,000 suicides in the United States annually with depressive disorder 15% of those hospitalized for major depressive disorder attempt suicide 15% of patients with severe primary major depressive disorder of at least 1 month s duration eventually commit suicide... 

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-... 

In a 10-week randomized, double-blind, study in 64 women with recurrent major depressive disorder, the dosage of topiramate was titrated up to 200 mg/day (1130). There were no serious adverse effects, including psychotic symptoms and suicidal acts. Adverse effects such as headache, fatigue, dizziness, and paresthesia were rated as mild. After 10 weeks there was weight loss, which was usually regarded as beneficial. 

Du L, et al. Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet 2000 96(1) 56-60. 

As already mentioned, the FDA s new warning is actually weaker than the Dear Healthcare Provider letter sent out by GlaxoSmithKline earlier in May 2006. The Paxil trials as disclosed in the letter showed an increased rate of suicidality in all ages of adults with major depressive disorder. 

The worst complication of major depressive disorder, of course, is suicide. Persons with major depressive disorder have a lifetime risk of suicide of about 15% (Guze and Robins, 1970). This highlights the fact that major depressive disorder is a potentially lethal illness. Also, this represents one of the major sources of preventable death. 

Nefazodone. Nefazodone is an antidepressant that inhibits neuronal uptake of serotonin and norepinephrine, Nefazodone is a 5-HT2 antagonist that is rapidly absorbed and has low bioavailabiiity (20%) because it undergoes first-pass metabolism. In March of 2004, the U.S. FDA issued a Pubhc Health Advisory that called attention to reports of both suicidal ideation and suicide attempts in children taking antidepressant drugs such as nefazodone for the treatment of major depressive disorder (MDD), Because of several cases of fiver toxicity, nefazodone (Serzone) was taken off the market in lune of 2004. An HPLC method with electrochemical detection has been published for the analysis of nefazodone. ... 

U.S. Food and Drug Administration. Reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. FDA Public Health Advisory, October 27, 2003. http //fda.gov/ cder/drug/advisory/mdd.html. Accessed January 15, 2004. 

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