Bipolar disorder

Bipolar disorder, previously known as manic-depressive illness, is a cyclical, lifelong disorder with recurrent extreme fluctuations in mood, energy, and behavior. Diagnosis requires the occurrence, during the course of the illness, of a manic, hypomanic, or mixed episode (not caused by any other medical condition, substance, or psychiatric disorder). 

Medical conditions, medications, and somatic treatments that may induce mania are shown in Table 69-1. 

See Chap. 70 for medical conditions, substance use disorders, and medications associated with depressive symptoms. 

Etiology and pathophysiology of bipolar disorder are shown in Table 69-2. 

dopamine 5-HT, serotonin LSD, lysergic acid diethylamide, MAOl, monoamine oxidase inhibitor, NE, norepinephrine PCP, 

The form of depression discussed previously is often referred to as major depressive disorder or unipolar depression, in contrast to bipolar or manic-depressive disorder. As these terms imply, bipolar syndrome is 

Lithium is readily absorbed from the gastrointestinal tract and completely distributed throughout all the tissues in the body. During an acute manic episode, achieving blood serum concentrations between 1.0 and 1.4 mEq/L is desirable. Maintenance doses are somewhat lower, and serum concentrations that range from 0.5 to 1.3 mEq/L are optimal. 

A major problem with lithium use is the danger of accumulation within the body.27 Lithium is not metabolized, and drug elimination takes place almost exclusively through excretion in the urine. Consequently, lithium has a tendency to accumulate in the body, and toxic levels can frequently be reached during administration. 

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The molten carbonate fuel ceU uses eutectic blends of Hthium and potassium carbonates as the electrolyte. A special grade of Hthium carbonate is used in treatment of affective mental (mood) disorders, including clinical depression and bipolar disorders. Lithium has also been evaluated in treatment of schizophrenia, schizoaffective disorders, alcoholism, and periodic aggressive behavior (56). 

Lithium ion is commonly ingested at dosages of 0.5 g/d of lithium carbonate for treatment of bipolar disorders. However, ingestion of higher concentrations (5 g/d of LiCl) can be fatal. As of this writing, lithium ion has not been related to industrial disease. However, lithium hydroxide, either dHectly or formed by hydrolysis of other salts, can cause caustic bums, and skin contact with lithium haHdes can result in skin dehydration. Organolithium compounds are often pyrophoric and requHe special handling (53). 

Other Drugs. Agents not considered to be CNS stimulants yet employed for the treatment of certain types of depression includes lithium carbonate for the treatment of bipolar disorder. In most patients, lithium is the sole agent used to control manic behavior and is very effective (see... 

Antipsychotic medications are indicated in the treatment of acute and chronic psychotic disorders. These include schizophrenia, schizoaffective disorder, and manic states occurring as part of a bipolar disorder or schizoaffective disorder. The co-adminstration of antipsychotic medication with antidepressants has also been shown to increase the remission rate of severe depressive episodes that are accompanied by psychotic symptoms. Antipsychotic medications are frequently used in the management of agitation associated with delirium, dementia, and toxic effects of both prescribed medications (e.g. L-dopa used in Parkinson s disease) and illicit dtugs (e.g. cocaine, amphetamines, andPCP). They are also indicated in the management of tics that result from Gilles de la Tourette s syndrome, and widely used to control the motor and behavioural manifestations of Huntington s disease. 

Bipolar disorder or manic depressive illness, refers to a severe mental illness characterized by recurring episodes of mania and depression. 

Bipolar Disorder (enzymatic activity reduced by therapeutic agents) ... 

Although lithium is not a true antipsychotic drug, it is considered with the antipsychotics because of its use in regulating the severe fluctuations of the manic phase of bipolar disorder (a psychiatric disorder characterized by severe mood swings of extreme hyperactivity to depression). During the manic phase, the person experiences altered thought processes, which can lead to bizarre delusions. The drug diminishes the frequency and intensity of hyperactive (manic) episodes. 

Ms. Brawn comes to the mental health clinic for a followup visit. She is taking lithium to control a bipolar disorder. Ms. Brown tells you that she is concerned because her hands are always shaking and sometimes I walk like I have been drinking alcohol. Explain how you would explore this problem with Ms. Brown. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Bredt DS, Snyder SEl Nitric oxide, a novel neuronal messenger. Neuron 8 3—11, 1992 Brouette T, Anton R Clinical review of inhalants. Am J Addict 10 79-94, 2001 Brown ES, Nejtek VA, Perantie DC, et al Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord4 406 11, 2002 Bushnell PJ, Evans EIL, Palmes ED Effects of toluene inhalation on carbon dioxide production and locomotor activity in mice. Fundam Appl Toxicol 5 971-977, 1983... 

Rates of smoking among patients with bipolar disorders and anxiety disorders (e.g., posttraumatic stress disorder, panic disorder) are also higher than those in the general population (Lasser et al. 2000), but there has been htde smdy of the factors associated with motivation to quit smoking or of smoking cessation interventions in these patient groups. 

Bipolar disorder usually begins in early adulthood and affects approximately 1% of the population. The cause of the disorder is largely unknown although hereditary factors play an important part, and major life events often precede the onset of the first episode of the disorder, and less obviously subsequent episodes. 

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. 

Drug treatment is a vital part of the management of bipolar disorder, both during episodes of depression or mania and as prophylaxis thereafter. Patients require explanation and education about the illness and about the treatments available, in order to be able to make informed choices and to avail themselves of the appropriate options fot treatment. 

The mood stabilizers were so called because they prevent recurrences of mood swings in people with bipolar disorder. The evidence for this is best with lithium, but is based on smdies carried out more than 20 years ago. However, recent naturalistic surveys tend to find that lithium is far less useful in general clinical practice than in research settings. Many patients discontinue lithium... 

In the case of carbamazepine the evidence suggests that its prophylactic efficacy is less than that of lithium (Greil and Kleindienst, 1999). For valproate there is no placebo-controlled evidence as yet to support its efficacy in the prophylaxis of bipolar disorder. The only large-scale study designed to elucidate this action was a failed trial in which neither lithium nor valproate was more effective than placebo in maintenance treatment over 2 years (Bowden et al, 2000). 

The symptoms of bipolar disorder and the side effects associated with its treatment have implications for the patient s health-related quality of life. The disorder itself has an impact upon mental and emotional wellbeing. Bipolar disorder also affects areas of life such as employment, social partnerships and independence. The side effects of treatment may further impair the quality of life. 

Health economic studies of bipolar disorder and Its treatment... 

The total costs are likely to reflect the efficacy of treatment. In one industry-sponsored study (Keck et al, 1996b) treatment with lithium or valproate was compared in relation to classical, mixed and rapid-cycling disorder. Treatment with lithium was associated with lower costs than treatment with valproate for classical bipolar disorder, but treatment with valproate was associated with lower costs than treatment with lithium for mixed and rapid-cycling disorders. This is in keeping with the evidence that valproate is more effective than lithium for certain patients with rapid-cycling disorder and probably also for certain patients with mixed affective states. However, these associations are a guide to predicting response to treatment but are not very specific. 

American Psychiatric Associarion (1994). Practice guideline for the treatment of patients with bipolar disorder. Am JPsychiatry 151 (suppl. 12), 1-36. 

Bauer MS, Shea N, McBride L, Gavin C (1997). Predictors of service utilization in veterans with bipolar disorder a prospective study. 

Maj M, Pirozzi R, Magliano L, et al (1998). Longterm outcome of lithium prophylaxis in bipolar disorder 5-year prospective study of 402 patients a lithium clinic. Am J Psychiatry 155,30-5. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

Major depressive episodes also occur in the context of bipolar disorder. The key difference is that persons with bipolar disorder also experience manic, hypomanic, and/or mixed episodes (see Chap. 36) during the course of their illness, whereas persons with MDD experience only major depressive episodes.3... 

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