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Suicide Attempts and Completions in Patients With Bipolar Disorder: Page 3 of 3

Suicide Attempts and Completions in Patients With Bipolar Disorder: Page 3 of 3

Substance use disorders
The active abuse of alcohol and/or drugs is an independent risk factor for suicide in patients with BD. Patients with a substance use disorder may be particularly impulsive and can be assumed to have greater impairment of judgment than they would without current substance abuse. It is now the standard of practice, in contradistinction to years past, to treat the substance use disorder and BD simultaneously.

Physicians are advised to have a particularly low threshold for hospitalizing patients with BD who are heavily abusing alcohol or extensively using dangerous substances—certainly if detoxification is necessary. Patients who habitually abuse alcohol or drugs and cannot be relied on to refrain from substance abuse constitute a highly nonadherent population. Even if medications are used as prescribed, it is wholly unreasonable to presume that these patients will respond well as outpatients.

Persons with BD have higher lifetime rates of alcohol and drug abuse than patients with any other Axis I disorder (other than patients with histories of primary substance use disorders). In the Epidemiologic Catchment Area (ECA) database, persons with BD have about 3 times the relative rate of alcohol and drug abuse than those with MDD. The ECA database revealed that 46% of the patients with BD had lifetime histories of alcohol abuse, 42% had histories of drug abuse, and 62.5% had histories of alcohol and/or drug abuse.8,19 (Please note that these are lifetime—not point—prevalences.)

Sample populations in epidemiological studies might be expected to be less severely ill than those comprising clinical samples. In large clinical samples, the rate of substance use disorders among individuals with BD has been reported to be as high as 70%.

Incorrect diagnosis and inappropriate treatment
A survey conducted by the National Depressive and Manic-Depressive Association in 2000 revealed that 60% of patients with BD had previously received a misdiagnosis of MDD, 26% had received a diagnosis of an anxiety disorder, and another fraction received a diagnosis of personality disorder.20 An average of 10 years passes between first contact with a physician and the correct diagnosis. During these years, patients may grow increasingly hopeless (a static risk factor for suicide), the illness generally becomes more severe, and patients are exposed to treatments (antidepressants) that may induce rapid cycling or otherwise adversely impact their course. These patients typically also suffer psychosocial damage that may be permanent. Consequently, because of the delay in making a correct diagnosis, the average person with BD is much more difficult to treat than he or she would have been if the proper diagnosis had been made at initial presentation. Incorrect diagnosis, maltreatment, and a delay in effective treatment greatly increase the risk of suicidal behavior and completed suicide.

The literature indicates that at least 40% of persons presenting with depressive symptoms have an illness that is bipolar in nature. This is consistent with well-designed studies indicating that the prevalence of BDII and other bipolar spectrum disorders with clinical presentations that clinicians may misdiagnose as simple depressive or anxiety disorders, are up to 2.4% for BDI, 4.8% for BDII, and 6.3% for cyclothymic disorder. The bipolar spectrum includes a minimum of 6% of the population, and some experts suggest that the percentage is much higher.21-26

Clinical significance of depressive mixed states or mixed depression
Depressive mixed state (DMX) is an MDE combined with manic/hypomanic symptoms. MDE with 3 or more features of hypomania other than euphoria or inflated self-esteem is expressed as DMX3.21,26-28 DMX is associated with a higher risk of suicidality than nonmixed depression.17,29,30 One contributing factor may be impulsivity associated with hypomanic activation.31

According to DSM-IV and the International Classification of Disease, 10th revision criteria, a patient with DMX has MDD. Particularly common symptoms in a DMX are irritability, distractibility, racing/crowded thoughts (often to the point of producing distress), psychomotor agitation, and increased activity.

The DMX is a nosological orphan. As a consequence, few psychiatrists have heard about it. Akiskal and Benazzi27 have presented validating findings indicating that patients with DMX tend to have family histories of BD and episodes of hypomania. Some patients have also had episodes of mania.

The DMX3 is a good indicator for BDII. Sensitivity and specificity increase in proportion to the number of symptoms of hypomania. Benazzi32 reported that there is a dose-response relationship between the number of hypomanic symptoms occurring in the context of DMX and a family history of BD. All patients meeting the criteria for DMX must be screened with care for a history of hypomania or mania.

The concept of DMX may be relevant to the debate over the capacity of antidepressants to induce suicidal ide- ation in children and adolescents. One can reasonably hypothesize that these drugs have the capacity to induce suicidal ideation in youths who have mixed depression or bipolar spectrum disorders.

Children and adolescents must be screened for the presence of DMX33 and a history of hypomania, even if it is only of 2 or 3 days' duration. The DSM-IV stipulation that a hypomanic syndrome must be of at least 4 days' duration is arbitrary. Empirically derived evidence indicates that episodes of only 2 days' duration are clinically significant. Two-day periods of hypomania are closely linked to a family history of bipolarity and a bipolar course is defined as epi- sodes lasting 4 or more days.21

There is more than 1 way to treat patients with mixed depression. A regimen of a sedating atypical antipsychotic agent with mood stabilizing properties followed, a few days to a week later, with the addition of an antidepressant, if necessary, may be effective.21 This regimen spares patients treatment with antidepressants in the absence of an antimanic and mood-stabilizing agent.

I might, for example, prescribe a weight-neutral atypical (since it is assumed that treatment will be long-term), along with the anticonvulsant lamotrigine titrated to 200 mg over 3 weeks because it produces nice antidepressant effects in many patients with bipolar disorder, and, because many patients have comorbid anxiety disorders, a high-potency benzodiazepine with antipanic properties. With this regimen, there is typically substantial improvement within a week and progressive improvement over 4 to 6 weeks.

Potential antisuicidal effects of lithium
Observations made in lithium clinics led investigators to suppose that this drug could have antisuicidal effects. Cipriani and colleagues34 conducted a meta-analysis of randomized trials assessing the efficacy of lithium relative to placebo and active treatments on the risk of suicide and intentional self-harm using the Cochrane Collaboration Depression, Anxiety and Neurosis controlled trials register. Thirty-two trials that included 1389 patients who received lithium and 2069 patients who received other agents provided data for the analysis. Patients who received lithium were less likely to commit suicide (odds ratio [OR] = 0.26; P = .01; 95% confidence interval [CI], 0.09 to 0.77). A composite measure of suicide and deliberate self-harm was also lower in patients treated with lithium (OR = 0.21; P = .0005; 95% CI, 0.08 to 0.50) and lithium was associated with a lower rate of death from all causes (OR = 0.42; P = .02; 95% CI, 0.21 to 0.87).

The authors concluded that the evidence "seems unequivocal that patients [treated] with lithium were much less likely to die of suicide or of another cause than patients given an alternative to lithium, whether the alternative was placebo or another compound." Lithium was associated with a reduction in the rate of suicide of about 60%, and risk of a composite measure of suicide and deliberate self-harm of about 70%.

It is important to recognize that the results of this key study strongly suggest, but do not prove, that lithium has mitigating effects on suicidal behavior. A study designed to prove that lithium has antisuicide effects relative to other treatments cannot be done for ethical reasons. It is also critical to appreciate that a great many more subjects have been treated with lithium in clinical trials than any other drug. Suicide has a low event rate in these trials.

A large number of subjects is required to attain sufficient statistical power necessary to obtain data indicating that a drug has antisuicide effects. Other effective treatments could have the same effect, but the composite number of subjects treated with these agents is too low to conduct a meta-analysis.

Nearly 19% of all patients with BD commit suicide in the absence of effective treatment. There are static factors that increase the risk of suicide and others that decrease it. However, the most important factors are dynamic in nature—those that have to do with mood state and change in mood state.

The erroneous diagnosis of BD as MDD, an anxiety disorder, or a personality disorder places patients at an increased risk for suicide because it may lead to the use of potentially harmful treatments and a delay in the institution of effective treatment. On the other hand, overlooking and withholding treatment for comorbid anxiety disorders and substance use disorders can also greatly increase the risk of suicide attempts and completed suicide.

Changes in nosological schemata occurring over the next decade, such as the redefinition of hypomania and the official recognition of the DMX, stand to positively affect clinical practice and decrease the rate of suicide associated with BD.



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