Subject suicidality

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... 

Assess the response to pharmacotherapy, especially with regard to suicidality and those symptoms that cause significant subjective distress and/or functional impairment. 

Arora, R. C. Meltzer, H. Y. (1989). Serotonergic measures in the brains of suicide victims 5-HT(2) binding sites in the frontal cortex of suicide victims and control subjects. Am. J. Psychiatry, 146, 730-6. 

No data are available on platelet NTE activity in exposed subjects, and little data on lymphocyte NTE activity. In one reported case of suicidal poisoning with chlorpyrifos, inhibition of lymphocyte NTE was correlated with the enzyme inhibition in peripheral nerves (Osterloh et al., 1983). In another case of attempted suicide with the same compound, inhibition of NTE in peripheral lymphocytes was associated with the development of delayed neuropathy (Lotti, 1986). However, the threshold of NTE inhibition required for delayed neuropathy remains undetermined (Lotti, 1987). Observations in occupationally exposed subjects are limited in number, and more research is needed to investigate the applicability of NTE as a biomarker of exposure to OP pesticides. 

G-protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders effects of diagnosis, suicide, and treatment at the time of death. J. Neurochem. 73, 1121-26. 

Chen, Y. W. and Dilsaver, S. C. Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol. Psych. 39 896-899,1996. 

Respiratory ejects Although preliminary studies did not reveal respiratory depressant effects at hypnotic doses of zaleplon in healthy subjects, observe caution if zaleplon is prescribed to patients with compromised respiratory function because sedatives/hypnotics have the capacity to depress respiratory drive. Depression As with other sedative/hypnotic drugs, administer zaleplon with caution to patients exhibiting signs or symptoms of depression. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdosage is more common in this group of patients therefore, prescribe the least amount of the drug that is feasible for the patient at any one time. 

One analysis (Angst and Wicki 1993) showed agoraphobia in 2.6% of control subjects, 2.8% of subjects with major depression, 7.4% of subjects with pure panic, and 28.0% of subjects with both panic disorder and major depression. Similarly, the attempted suicide rate was 3.5% among control subjects, 5.0% in subjects with pure panic, 13.0% in subjects with depression without panic, and 28.9% in patients with both panic disorder and major depression. These data underline the importance of recognizing and treating comorbid depression in patients with panic disorder. 

Leon AC, Keller MB, Warshaw MG, et al. Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects. Am J Psychiatry 1999 156 195-201. 

Randrup et al. (55) first postulated a role for dopamine in depressive disorders. More recently, a reanalysis of the data from several groups has found evidence for a bimodal distribution of CSF homovanillic acid (HVA) levels in depressed patients, with one group comparable with normal control subjects and the other with decreased levels (56). Roy and colleagues (57) also reported on the potential predictive value of lower urinary HVA output in depressed patients who attempted suicide versus those who did not. Both reports indicate a decreased turnover in dopamine. 

None of these definitions is ideal. Patients may be hospitalized for a suicide gesture or a co-morbid condition such as a severe personality disorder or substance abuse rather than solely on the basis of their depression severity. A score of 25 or higher on the 17-item HDRS is the most commonly used cutoff to distinguish nonsevere from severe depression. This approach, however, is subject to the possibility of inflation of scores to qualify patients for the trial. 

Of the 38 subjects tested, 27 showed the predicted shift (13 of 19 in the Decrease condition and 14 of 19 in the Increase condition), and 11 did not,/> <. 01 by the sign test. Five subjects in each condition showed no shift, whereas one subject in the Decrease condition, a suicidal type, showed a shift opposite from prediction. 

Human toxicity data, especially the median lethal dose, is extrapolated from animals or from accidental poisoning, homicides and suicides. Extrapolations from animal data are educated estimates which consider the differences in species and building in a safety factor. If a lethal dose is 10 mg/kg in a rat and we consider a human to be 10 times more sensitive 1 mg/kg will have another 10-fold safety margin. Animal testing also involves using what may seem as ridiculous doses in order to cover the safety factor. To find a statistically valid effect which occurs once in one million subjects, several million animals would have to be used, which is exhorbitantly... 

Mechanism-based inhibitors (also known as suicide inhibitors or as kcat inhibitors) are actually substrates for their target enzymes. A reactive group is only revealed by enzyme action it is therefore not subject to hydrolysis until it has been revealed in the vicinity of the enzyme. The ability of the inhibitor then to inactivate the enzyme will depend upon relative rates of (a) covalent bond formation with the enzyme, (b) diffusion of the reactive entity away from the enzyme, and (c) hydrolysis. 

Diseases such as schizophrenia and/or malvaria (Hoffer and Osmond, 1962), are contraindications for the use of psychedelics, because subjects who have them are unlikely to have psychedelic reactions and are much more likely to have prolonged depressions and other psychotic reactions. These can lead to severe anxiety or panic, to suicide, and, very rarely, to other violent acts. Recurrences may occur several months later, but it is difficult to decide whether this is a recurrence of the LSD reaction or a resurgence of schizophrenia. 

Some studies have shown increased risks of violent death and depression in subjects with reduced serum cholesterol concentrations. Serum and membrane cholesterol concentrations, the microviscosity of erythrocyte membranes, and platelet serotonin uptake have been determined in 17 patients with hypercholesterolemia (21). There was a significant increase in serotonin transporter activity only during the first month of simvastatin therapy. This suggests that within this period some patients could be vulnerable to depression, violence, or suicide. This is an important paper, in that it explains why mood disorders are not regularly seen in clinical trials with statins, as has been summarized in a recent review (3). 

Just how safe the barbiturates are is subject to much debate. For one thing, in high doses, they are lethal, the reason that for many years barbiturate overdose was a common way by which people committed suicide. In addition, the rebound produced... 

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