Depression in bipolar disorder

Disturbances of sleep are typical of mood disorders, and belong to the core symptoms of major depression. More than 90% of depressed patients complain of impaired sleep quality [60], Typically, patients suffer from difficulties in falling asleep, frequent nocturnal awakenings, and early morning awakening. Not only is insomnia a typical symptom of depression but, studies suggest, conversely, insomnia may be an independent risk factor for depression. In bipolar disorders sleep loss may also be a risk factor for the development of mania. Hypersomnia is less typical for depression [61] and, in contrast to insomnia, may be related to certain subtypes of depression, such as seasonal affective disorder (SAD). 

Zornberg GL, Pope HG Jr Treatment of depression in bipolar disorder new directions for research. J Clin Psychopharmacol 13 397-408, 1993... 

This report illustrates the difficulty of treating depression in bipolar disorder with antidepressants. The presence of a mood stabilizer did not prevent the manic episode that emerged during venlafaxine treatment, and it is in any case difficult to know whether the mania was in fact due to the venlafaxine or instead represented a spontaneous mood swing. 

Unstable mood, especially depression, in bipolar disorder... 

One or more manic or hypomanic episodes with one or more major depressive episodes generally constitute the diagnosis of bipolar I disorder. Depression in bipolar disorder meets diagnostic criteria for major depression, with the exceptions of shorter duration and increased frequency. Depending on the cmrent presentation, bipolar disorder is subclassified as one of the following (DSM-IV) ... 

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). 

Affective (mood) disorders are characterized by changes in mood. The most common manifestation is depression, arranging from mild to severe forms. Psychotic depression is accompanied by hallucinations and illusions. Mania is less common than depression. In bipolar affective disorder, depression alternates with mania. 

The primary treatment for depressive episodes in bipolar disorder is mood-stabilizing agents, often combined with antidepressant drugs. 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

In clinical psychiatric terms, the affective disorders can be subdivided into unipolar and bipolar disorders. Unipolar depression is also known as psychotic depression, endogenous depression, idiopathic depression and major depressive disorder. Bipolar disorder is now recognised as being heterogeneous bipolar disorder I is equivalent to classical manic depressive psychosis, or manic depression, while bipolar disorder II is depression with hypomania (Dean, 2002). Unipolar mania is where periods of mania alternate with periods of more normal moods. Seasonal affective disorder (SAD) refers to depression with its onset most commonly in winter, followed by a gradual remission in spring. Some milder forms of severe depression, often those with an identifiable cause, may be referred to as reactive or neurotic depression. Secondary depression is associated with other illnesses, such as neuro-degenerative or cardiovascular diseases, and is relatively common. 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

The serotonergic system has long been thought to play a role in major depression and bipolar disorders, although the exact mechanisms are yet to be determined 889... 

Both genetic and nongenetic factors play roles in the transmission of mood disorders. The familial nature of mood disorders is well established. Studies over the past 20 years have consistently documented higher rates of mood disorder in the relatives of individuals with major depression and bipolar disorder than in relatives of healthy controls [6,7], The familial aggregation of mood disorders is the outcome of both genetic and environmental factors. 

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. 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Shock Therapy. Insulin coma treatments were used in the early 1900s but offered no tangible improvement. Electroconvulsive therapy (ECT) arose in the 1930s and 1940s and was the hrst treatment to provide some relief from psychosis. However, its effects are only temporary and it proved too costly for continuous use. ECT continues to have some use for life-threatening catatonia, but it is mainly used to treat refractory depression or bipolar disorder. 

Lithium chloride (Li" + Cl —> LICl) is used as an antidepressant, especially in the treatment of manic depression and bipolar disorders. 

Psychosis or mania Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible individuals. The sustained-release formulation of bupropion is expected to pose similar risks. There were no reports of activation of psychosis or mania in clinical trials conducted in nondepressed smokers. 

The most common mood disorders are major depression (unipolar depression) and manic-depressive illness (bipolar disorder). Major depression is a common disorder that continues to result in considerable morbidity and mortality despite major advances in treatment. Approximately 1 in 10 Americans will be depressed during their lifetime. Of the 40,000 suicides occurring in the United States each year, 70% can be accounted for by depression. Antidepressants are now the mainstay of treatment for this potentially lethal disorder, with patients showing some response to treatment 65 to 80% of the time. 

There is no empirical evidence available for clinical use in children and adolescents. Yet, Hypericum seems to be used for the treatment of mild to moderate depression in the young (Walter et ah, 2000). St. John s wort should be avoided in young patients with severe depression and bipolar disorder (given the lack of adult data about effectiveness and risk of manic induction, respectively) and in those who have significant suicide risk. Treatments of proven efficacy (e.g., SSRIs, mood stabilisers) should be preferred in these cases. However, St. John s wort may be considered in cases of unipolar depression where conventional treatments have failed and prior to the use of combinations of drugs that have an increased risk of side effects and whose efficacy has not been demonstrated. 

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