Lithium suicide

The antipsychotic dru are used cautiously in patients exposed to extreme heat or phosphorous insecticides and in those with respiratory disorders, glaucoma, prostatic hypertrophy, epilepsy, decreased renal function, lactation, or peptic ulcer. The antipsychotic drags are used cautiously in elderly and debilitated patients because these patients are more sensitive to the antipsychotic dragp. lithium is used cautiously in patients who are in situations in which they may sweat profusely and those who are suicidal, have diarrhea, or who have an infection or fever. 

Electroconvulsive therapy (ECT) is the application of prescribed electrical impulses to the brain for the treatment of severe depression, mixed states, psychotic depression, and treatment-refractory mania in patients who are at high risk of suicide. It also may be used in pregnant women who cannot take carbamazepine, lithium, or divalproex. 

Increasing evidence shows an effect of lithium on suicidal behavior that is superior to other mood-stabilizing drugs.28 Lithium reduces the risk of deliberate self-harm or suicide by about 70%. 

Following initial assessment, including evaluation of potential suicidality, support systems, and need for inpatient versus outpatient treatment, MW was hospitalized briefly, then followed in the community on medication along with psychotherapy. She has abstained from illicit substances and has returned to her job. She has responded well to treatment with sustained-release lithium carbonate 900 mg once daily at bedtime with a snack. Steady-state 12-hour serum lithium concentrations have stabilized at 0.9 mEq/L (0.9 mmol/L). She now returns to clinic for routine followup. She has tolerated the lithium except for a mild tremor and a gain of 7 pounds (3.2 kg). She is willing to accept these side effects for now, but asks about how long she must take medication since she is now feeling well. 

The development of lithium-specific electrodes has assisted greatly in monitoring patient compliance. The toxicity profile of lithium carbonate is now well established and the drug is safely administered and well tolerated. It is of limited use in other psychiatric disorders such as pathological aggression, although additional benefit may also include a reduction in actual or attempted suicide. 

Lithium was the first established mood stabilizer and is still considered a first-line agent for acute mania and maintenance treatment of both bipolar I and II disorders. It is the only bipolar medication approved for adults and children 12 years and older. Long-term use of lithium reduces suicide risk. Patients with rapid cycling or mixed states may not respond as well to lithium monotherapy as to some anticonvulsants. 

Lithium is effective for acute mania, but it may require 6 to 8 weeks to show antidepressant efficacy. It may be more effective for elated mania and less effective for mania with psychotic features, mixed episodes, rapid cycling, and when alcohol and drug abuse is present. Maintenance therapy is more effective in patients with fewer episodes, good functioning between episodes, and when there is a family history of good response to lithium. It produces a prophylactic response in up to two-thirds of patients and reduces suicide risk by eight- to 10-fold. 

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. 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Baldessarini, R.J., Tondo, L., Hennen, J. Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders. J. Clin. Psychiatry 60 (SuppL 2), 77-84, 111-116, 1999. 

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... 

For more than 40 years, lithium has been the standard drug therapy for bipolar disorder, primarily because of the quantity and the quality of evidence supporting its role as an effective maintenance and prophylactic treatment. This latter point is a very important consideration, given the recurrent nature of this disorder. Thus, clinicians must choose the optimal strategy for acute treatment with the realization that most patients will need to continue drug therapy indefinitely. In addition, there is support for maintenance lithium s beneficial impact on the suicide rate in bipolar patients ( 73, 74). The author of these reports notes that the lower suicide risk associated with lithium treatment may be due to the following ... 

Coppen et al. (191) evaluated the status of 104 bipolar or unipolar recurrent patients after 10 years of lithium maintenance to assess mortality rate, in part because of reports indicating unusually high rates, with many deaths attributed to suicide. Compliance was very high, with only 6% discontinuing lithium therapy, and patients also received adjunctive antipsychotic and/or antidepressants when clinically indicated. No patient died of suicide during this period, in contrast to the results in lithium noncompliant patients. The authors concluded that the absence of suicide resulted from the significant reduction in morbidity achieved by the careful administration of lithium. 

Nilsson A. Lithium therapy and suicide risk. J Clin Psychiatry 1999 60(suppl 2) 85-88. 

Tondo L, Baldessarini RJ. Reduced suicide risk during lithium maintenance treatment. J Clin Psychiatry 2000 61(suppl 9) 97-104. 

Links et al. (236) reported a small, blind, crossover study in BPD patients treated with lithium, desipramine, and placebo. Whereas eight of 13 patients responded to desipramine, six of 12 also responded to placebo. Of those patients with high scores for anger and suicide symptoms, four of 11 responded to desipramine, in comparison with five of six with placebo. Finally, another trial also found CBZ to be beneficial ( 237). 

Bocchetta A, Chillotti C, Carboni G, Oi A, Ponti M, Del Zompo M. Association of personal and familial suicide risk with low serum cholesterol concentration in male lithium patients. Acta Psychiatr Scand 2001 104 37-41. 

It is frequently claimed that lithium reduces the risk of suicide in people with manic depression. Meta-analyses of numerous diverse studies claim to show that people with manic depression or depression who take lithium have lower suicide rates than people who do not (Baldessarini et al. 2006). However the studies included in these analyses yield conflicting results. For example, a large British study found that people taking lithium had suicide rates that were 36 times higher than general population rates (Norton Whalley 1984). In addition, those studies that find an association between lithium and reduced rates of... 

The least biased evidence on whether lithium and other mood stabilisers have antisuicidal properties comes from randomised controlled trials and this is negative. A large amount of data from studies of drug treatment of acute mania and relapse prevention found no difference in rates of suicide or suicide attempts between patients randomised to take mood stabilisers, including lithium, and those randomised to placebo (Storosum et al. 2005). 

Baldessarini, R. J., Tondo, L., Davis, P., Pompili, M., Goodwin, R K., Hennen, J. 2006, Decreased risk of suicides and attempts during long-term lithium treatment a meta-analytic review, Bipolar.Disord., vol. 8, no. 5, Pt 2, pp. 625-639. 

Tondo, L., Baldessarini, R. J., Hennen, J., Floris, G., Silvetti, E, Tohen, M. 1998, Lithium treatment and risk of suicidal behavior in bipolar disorder patients, J.Clin.Psychiatry, vol. 59, no. 8, pp. 405-414. 

In a systematic review of 32 randomized trials in which 1389 patients took lithium and 2069 took another agent (carbamazepine, divalproex, lamotrigine, or the antidepressants amitriptyline, fluvoxamine, mianserin, and maprotiline), among the seven studies that reported suicides, lithium-treated patients had significantly fewer completed events (242). These included two suicides on lithium (out of 503, 0.4%) and 11 suicides on other agents (two placebo, two amitriptyline, six carbamazepine, and one lamotrigine, out of a total of 601,1.8%) (OR = 0.26 95% Cl = 0.09, 0.77). 

There was a similar pattern in an observational study of all lithium prescriptions and recorded suicides in Demark from 1995 tol999 inclusive (245). Purchasing lithium was associated with a higher rate of suicide, but purchasing lithium at least twice was associated with a significantly lower risk (0.44 95% Cl = 0.28, 0.70). In other words, lithium is prescribed for patients who are at high risk of suicide, but continuing to take lithium appears to be protective. These studies have laid the foundations for a current adequately powered, prospective study of the purported anti-suicide effect of lithium (246). 

Others have concluded that withdrawal mania is a major and sinister complication of the everyday use of lithium (459). Withdrawal of effective lithium therapy was associated with an increased risk of suicide and suicidal acts, especially during the first 12 months. Gradual withdrawal (over 15-30 days) was associated with half the rate of suicidal acts compared with more rapid withdrawal (strong trend toward statistical significance) (460). 

When the Marseilles Poisons Centre analysed information on lithium overdose between 1991 and 2000, in addition to an unspecified number of suicide attempts and accidental poisonings in children, the next most frequent reports were prescription misinterpretation (n = 43), dehydration in the elderly (n = 35), renal insufficiency (n = 15), and diuretic interactions (n = 8) (533). 

The 2000 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System listed six lithium-related deaths (four cases of intentional suicide and two of therapeutic error) and two other deaths in which lithium was not listed as the primary cause (534). A total of 4663 lithium-related exposures were reported, in which death was the outcome in 13 and a major hfe-threatening event or cause of significant disability in 267. 

A study of drug intoxication in the south of Brazil reported 2938 cases of drug ingestion, 25 of which involved lithium (including 14 suicide attempts) (541). 

Of 133 patients 40 who had begun treatment with lithium died over an observation period of 16 years. Suicide (in 11 cases) was twice as common as in the general population, but it was more likely to occur in lithium noncompliant patients (542). It is important to be aware that suicidal behavior is actually reduced in patients who are compliant with long-term lithium therapy (although still somewhat higher than in the general population). 

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