Suicide in depression

The possibility of suicide in depressed patients remains during treatment and until significant remission occurs. Patients should not have easy access to large... 

The side effects of antidepressants, sometimes very unpleasant, olten lead patients to interrupt their treatment or to reduce the drug dose, which involves a great risk in view of the high relapse rate and danger of suicide in depression. The newer antidepressants, such as trazodone, fluoxetine and other SSRIs and moclobemide, are characterized by better tolerability and lower toxicity and are therefore preferred in the treatment of outpatients and elderly patients (Rudorfer and Potter, 1989). A detailed list of general and specific common side effects associated with the newer generation of antidepressants is seen in Table 1.7. 

Moller HJ Evidence for beneficial effects of antidepressants on suicidality in depressive patients A systematic review. Eur Arch Psychiatry Clin Neurosci 2006 256(6) 329. [PMID 16783501]... 

Sakinofsky I Treating suicidality in depressive illness. Part 2 Does treatment cure or cause suicidality Can J Psychiatry 2007 52(6 Suppl 1) 85S. 

Depression occurring as part of bipolar disorder may be severe and accompanied by ideas of guilt and hopelessness, an inability to function at work because of poor concentration and psychomotor retardation or agitation, poor judgement and suicidal ideation. The lifelong risk of suicide in people with this condition is as high as 15%. Factors associated with suicide risk include alcohol misuse, marital separation or divorce, living alone and unemployment, and these are all common secondary consequences of the illness. 

So far, evidence for abnormal peripheral (Elliott 1992) or central (Horton 1992) monoamine function in depression is equivocal, and no consistent biochemical markers have emerged to provide a firm link between the two (Table 20.2). One widely cited finding is that subjects who have attempted violent suicide form a neurochemically distinct group because the concentration of the 5-HT metabolite, 5-HIAA, in their CSF is lower than normal, suggesting that a deficit in 5-HT release is associated with suicide... 

Pediatric patients should be observed closely for suicidality, worsened depression, agitation, irritability, and unusual changes in behavior, especially during the initial few months of therapy or at times of dosage changes. Furthermore, families and caregivers should be advised to monitor patients for such symptoms. 

Suicidal thoughts are one of the symptoms of depression. Paradoxically, one of the best-publicized dangers of SSRIs is their potential to increase the risk of suicide. This heightened risk is especially well established for children, adolescents and young adults. In their most recent analysis of the data, the FDA concluded that, when compared to placebos, SSRIs double the risk of suicidal thoughts and behaviour in depressed patients up to the age of 24/ There also seems to be an increased risk for people who are older than 24, but the interpretation of these data is still disputed.8... 

Healy D, Langmark C and Savage M (1999). Suicide in the course of the treatment of depression. Journal of Psychopharmacology, 13, 94-99. 

In the past several decades there has been increased incidence of depression, which motivated Gerald Klerman to describe this era as the age of melancholia [5], The lifetime prevalence of depression in the U.S. is higher in women (21.3%) than in men (12.7%). Although the rates of major depression vary across the world, data from fifty countries support the notion that this disease is the fourth leading cause of disability worldwide (second in developed countries) [3]. Longitudinal studies verify that the typical course of the disease is recurrent, with periods of recovery and periods of depression symptoms however, approximately 17% of patients have a chronic unremitting disease [6], Depression is the major cause of suicidal behavior and the rate of suicidal attempts has been estimated to be around 56% in depressed patients [7]. 

The symptom most highly correlated with suicidal behavior in depression is hopelessness. 

In depressed patients, cortical-hypothalamic-pituitary-adrenal axis hyperactivity can be explained by the hypersecretion of CRF, and secondary pituitary and adrenal gland hypertrophy. Impaired negative feedback at various CNS sites, including the hippocampus and pituitary are also likely to contribute. Downregulation of hippocampal mineralocorticoid receptors and expression is reported in depressed suicides [50]. In bipolar disorder, hyperactivity of the cortical-hypothalamic-pituitary-adrenal axis has been observed [51]. This increase in cortical-hypothalamic-pituitary-adrenal axis activity has also been observed in mixed mood states, mania and in depression in rapidcycling patients. Partial reversal of HPA overactivity is associated with treatment and recovery from depression. 

Mann, J. J., Malone, K. M., Sweeney, J. A. et al. Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients. Neuropsychopharm. 15 576-586,1996. 

If a family member notices any of the symptoms previously mentioned in a loved one, then it may be that the loved one is depressed and should be evaluated by a mental health professional. If a loved one is expressing suicidal thoughts, or it is discovered that he or she has put his or her affairs in order (has sold or given away significant amounts of personal property, written a will, settled debts, etc.), then it would be critical to get help for that person as quickly as possible. Suicide is a major concern with people who abuse drugs, since a majority of suicides in the United States are attempted under the influence of drugs or alcohol. 

Anorexia nervosa sufferers can exhibit sudden angry outbursts or become socially withdrawn. One in ten cases of anorexia nervosa leads to death from starvation, cardiac arrest, other medical complications, or suicide. Clinical depression and anxiety place many individuals with eating disorders at risk for suicidal behavior. 

Lithium is the simplest therapeutic agent for the treatment of depression and has been used for over 100 years—lithium carbonate and citrate were described in the British Pharmacopoeia of 1885. Lithium therapy went through periods when it was in common use, and periods when it was discouraged. Finally, in 1949, J.J.F. Cade reported that lithium carbonate could reverse the symptoms of patients with bipolar disorder (manic-depression), a chronic disorder that affects between 1% and 2% of the population. The disease is characterized by episodic periods of elevated or depressed mood, severely reduces the patients quality of life and dramatically increases their likelihood of committing suicide. Today, it is the standard treatment, often combined with other drugs, for bipolar disorder and is prescribed in over 50% of bipolar disorder patients. It has clearly been shown to reduce the risk of suicide in mood disorder patients, and its socioeconomic impact is considerable—it is estimated to have saved around 9 billion in the USA alone in 1881. 

It has been hypothesized that depression could arise from a pathological enhancement of 5-HT2 receptor function. This view would concur with the observations that the functional activity of 5-HT2 receptors on the platelet membrane is enhanced in depression and the increase in the density of 5-HT2 receptors in the frontal cortex of brains from suicide victims. It is possible that enhanced 5-HT2 receptor function is associated primarily with anxiety, a common feature of depression, and that the increased activity of the 5-HT2 receptors results in an attenuation of the functioning of S-HT receptors thereby resulting in the symptoms of depression. Whether this change in the activity of S-HT receptors is due to direct effects of the altered 5-HT2 receptor function is uncertain. There is evidence that hypercortisolaemia, which is a characteristic feature of depression, reduces the activity of these receptors probably through central glucocorticoid type 2 receptors. Clearly further research is needed to determine the precise interaction between the 5-HT2 and 5-HTi receptor types. 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Suicide In those patients in whom depression accompanies anxiety, suicidal tendencies may be present, and protective measures may be required. 

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). 

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