Unipolar illness

The study of antidepressant maintenance medications for patients with unipolar MDD has been historically neglected. Such neglect is puzzling. Considering that multiple recurrences may well be the sine qua non for unmedicated patients with manic depression [Coryell and Winokur 1982 NIMH/ NIH Consensus Development Panel 1985 Prien et al. 1984 Suppes et al. 1991 Zis and Goodwin 1979 Zis et al. 1980] and that unipolar illness is pathophysiologically similar to bipolar disorder in many important respects, recurrences could have been presumed to be innate. 

Blumenthal RL, Egeland JA, Sharpe L, et al. Age of onset in bipolar and unipolar illness with and without delusions or hallucinations. Compr Psychiatry 1987 28 547-554. 

Greater adherence to treatment Pure form of bipolar illness Endogenomorphic unipolar illness Family history of bipolar illness Mania followed by depression Previous good response to treatment... 

I Although the drug enjoys a reputation for efficacy in recurrent unipolar illness and treatment-resistant depressive disorder, there is little convincing evidence to support this. 

Studies of health economics in the UK and the USA in unipolar depressive illness show... 

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. 

Phases of Bipolar Illness. The depressive phase of bipolar illness is virtually indistinguishable from unipolar MDD and the diagnostic criteria for a major depressive episode (refer to Table 3.2) are used to diagnose bipolar depression as well. The clinical presentation of bipolar depression often resembles atypical depression, which is characterized by severe fatigue and oversleeping. 

An episode of bipolar depression is virtually indistinguishable from that of unipolar depression. The key is to gather a careful history of the patient s premorbid functioning, earlier episodes of illness, and family psychiatric illness. This information should be gathered from the patient, as well as family members and friends. Previous episodes of full-blown mania seldom go unreported however, prior hypo-manic episodes are often unrecognized not only by the patient but by friends and family as well. One should inquire about periods of decreased need for sleep (as... 

Between the mood disorders and schizophrenia lies schizoaffective disorder. Taking both unipolar and bipolar forms, schizoaffective disorder is manifested by periods of mood disturbance accompanied by psychotic symptoms that persist even when the mood disturbance has resolved. Schizoaffective disorder typically produces a greater degree of social dysfunction than bipolar illness but less impairment than schizophrenia. 

The diagnosis of mania is made on the basis of clinical history plus a mental state examination. Key features of mania include elevated, expansive or irritable mood accompanied by hyperactivity, pressure of speech, flight of ideas, grandiosity, hyposomnia and distractibility. Such episodes may alternate with severe depression, hence the term "bipolar illness", which is clinically similar to that seen in patients with "unipolar depression". In such cases, the mood can range from sadness to profound melancholia with feelings of guilt, anxiety, apprehension and suicidal ideation accompanied by anhedonia (lack of interest in work, food, sex, etc.). 

Manic-depressive illness connotes a psychotic disorder of affect that occurs episodically without external cause. In endogenous depression (melancholia), mood is persistently low. Mania refers to the opposite condition (p. 234). Patients may oscillate between these two extremes with interludes of normal mood. Depending on the type of disorder, mood swings may alternate between the two directions (bipolar depression, cyclothymia) or occur in only one direction (unipolar depression). 

Bipolar disease, or recurrent unipolar disease may be manic-depressive illness. This disease can manifest as typical bipolar disease, with alternating depressive and manic episodes, or as recurrent depression (or more rarely recurrent mania). The age of onset and frequency of recurrence may be highly variable, with at best a single episode, where the disease may be suspected from family history. The intensity of individual episodes may vary from the maximal intensities of depression, also called melancholia, or mania justifying rapid hospitalisation to barely pathological mood swings, where it is an alternation and... 

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. 

One of the advances in descriptive diagnosis is the increasingly clear distinction between unipolar and bipolar illnesses. In bipolar illness there is primarily... 

I. F. Small et al. 1986), and in our experience the same may hold true for some young patients with schizophrenia. However, confounding variables such as age and gender have not been addressed in these studies. In patients with major depressive disorder, we found no relation between seizure threshold and unipolar versus bipolar or psychotic versus nonpsychotic subtypes. Similarly, Coffey et al. (1995a) found no correlation between initial seizure threshold and severity of depressive illness or the unipolar-bipolar distinction. Finally, we found that history of ECT did not predict seizure threshold (Krueger et al. 1993). 

FIGURE 20-1. life course of illness in unipolar depression. NIH = National Institutes of Health. 

Glen AIM, Johnson AL, Shepherd M Continuation therapy with lithium and amitriptyline in unipolar depressive illness a randomized double-blind controlled trial. Psychol Med 14 37-50, 1984... 

Kahn NH, Shelton SJ Defensive behaviors in infant rhesus monkeys environmental cues and neurochemical regulation. Science 243 1718-1721, 1989 Kahnowsky LB, Kennedy F Observations in electric shock therapy apphed to problems of epilepsy. J Nerv Ment Dis 98 56-67, 1943 Kampen D, Sherwin B Estrogen use and verbal memory in healthy postmenopausal women. Obstet Gynecol 83 979-983, 1994 Kane JM, Quitkin FM, Rifkin A, et al Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar 11 illness a prospective placebo-controlled comparison. Arch Gen Psychiatry 39 1065-1069, 1982 Kaneno S, Komatsu H, Fukamauchi F, et al Biochemical basis of antidepressant-effect of low dose of sulpiride. Japanese Journal of Psychiatry and Neurology 45 131-132, 1991... 

Lithium has been proven effective for acute and prophylactic treatment of both manic and depressive episodes in patients with bipolar illness (American Psychiatric Association 2002). However, patients with rapid-cycling bipolar disorder (i.e., patients who experience four or more mood disorder episodes per year) have been reported to respond less well to lithium treatment (Dunner and Fieve 1974 Prien et al. 1984 Wehr et al. 1988). Lithium is also effective in preventing future depressive episodes in patients with recurrent unipolar depressive disorder (American Psychiatric Association 2002) and as an adjunct to antidepressant therapy in depressed patients whose illness is partially refractory to treatment with antidepressants alone (discussed in Chapter 2). Furthermore, hthium may be useful in maintaining remission of depressive disorders after electroconvulsive therapy (Coppen et al. 1981 Sackeim et al. 2001). Lithium also has been used effectively in some cases of aggression and behavioral dyscontrol. 

Kane JM, Quitkin FM, Rifkin A, et al. Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness. Arch Gen Psychiatry 1982 39 1065-1069. 

Coppen A, Gupta R, Montgomery S, et al. A double blind comparison of lithium carbonate and Ludiomil in the prophylaxis of unipolar affective illness. Pharmacopsychiatry 1976 9 94-99. 

Bipolar disorder (manic-depressive illness) represents one of the most dramatic presentations in all of medicine and simultaneously poses one of the more difficult therapeutic challenges. It is characterized by mania or hypomania, alternating irregularly or intermingling with episodes of depression however, a small group (approximately 1%) may only experience recurrent manic episodes (i.e., unipolar mania). The estimated risk of developing a bipolar disorder is 0.5% to 1%, and the incidence of new cases per year is in the range of 0.01 % for men and 0.01 % to 0.03% for women (1). Bipolar spectrum can be conceived of as a continuum of more to less severe clinical presentations ... 

Baastrup and associates (6) studied manic-depressive and recurrently depressed Danish patients who had been successfully stabilized on lithium for at least 1 year. This ensured that subjects had the type of illness that is helped by lithium, and that they could tolerate the treatment. Because it was a prospective, well-controlled, random-assignment, double-blind study (i.e., class I), potential biases were effectively eliminated. These authors demonstrated a dramatic and positive effect for lithium when compared with placebo. None of the patients who received lithium over a 5-month period relapsed, whereas 55% of the bipolar and 53% of the unipolar patients on placebo did so. 

Zarate and his collaborators (301) conducted a systematic follow-up study, evaluating the number of hospitalizations in the 5 years before clozapine compared with the rehospitalization rate while on this agent. These authors found that monotherapy with clozapine reduced both the number of episodes and rehospitalizations in 17 previously severely ill affective patients. The yearly rate before clozapine was 0.8 1.2 and after clozapine 0.4 1.2, a difference that was statistically significant. Rehospitalization rates were lowest in the schizophrenic, schizoaffective bipolar, and schizoaffective depressed patients, whereas unipolar and bipolar depressed patients had the highest relapse rate. 

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