Affective disorders Mania

Lithium, whose proprietary names include Eskalith, Lithane, Lithonate, and others, is administered as lithium carbonate and used for treatment of the manic phase of affective disorders, mania, and manic-depressive illness. It is postulated to act by enhancing reuptake of catecholamines, thereby reducing their concentration in the neuronal junction. This produces a sedating effect on the central nervous system. Lithium also modulates the distribution of sodium, calcium, and magnesium in nerve cells, which reduces the rate of glucose metabolism that effects nerve function. The actual mechanism of action of lithium in affecting mania remains theoretical. 

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. 

Cookson JC, Sachs GS (1999). Lithium clinical use in mania and prophylaxis of affective disorders. In Buckley PF, Waddington JL, eds, Schizophrenia and Mood Disorders The New Drug Therapies in Clinical Practice. Oxford Butterworth Heinemann. 

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. 

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. 

Table 12.1. Symptoms of the affective disorders major depression and mania. 

Neurochemical theories for the affective disorders propose that there is a link between dysfunctional monoaminergic synapses within the central nervous system (CNS) and mood problems. The original focus was the neurotransmitter noradrenaline, or NA (note noradrenaline is called norepinephrine, or NE, in American texts). Schildkraut (1965) suggested that depression was associated with an absolute or relative deficiency of NA, while mania was associated with a functional excess of NA. Subsequently, another monoamine neurotransmitter 5-hydroxytryptamine (5-HT), or serotonin, was put forward in a rival indoleamine theory (Chapter 2). However, it was soon recognised that both proposals could be reconciled with the available clinical biochemical and pharmacological evidence (Luchins, 1976 Green and Costain, 1979). 

Affective disorders A group of psychoses characterised by a pathological and long-lasting disturbance of mood or affect. They include the unipolar disorders (e.g., depression and mania), and bipolar disorders (e.g., manic depression). 

Unipolar disorder An affective disorder characterised by chronic dysphoria. The two contrasting forms of unipolar disorder are major depression and mania. 

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). 

One model of an ionic mechanism of action of Li+ in affective disorders has been proposed, in which the receptors for Li+ are ion channels and cation coenzyme receptor sites, and in which the presence of intracellular Li+ in excitable cells results in the displacement of exogenous Na+ and/or other intracellular cations [13]. It has been suggested that this could lead to a decrease in the release of neurotransmitters alternatively it may be that this intracellular Li+ is altering a preexisting, disease-related electrolyte imbalance [14]. A number of observations of such imbalances in affective disorders have been made depression is associated with elevated levels of intracellular Na+ [15] retention of Li+ is observed in manic-depressive patients prior to an episode of mania [ 16] and Na+/K+ activity is defective during both mania and depression [17]. 

Bipolar Affective Disorder. A class of disorders that features mood swings from great highs (mania) to great lows (depression). 

In the bipolar affective disorders (BPADs), periods of normal mood are interspersed with episodes of mania, hypomania, mixed states, or depression. BPAD differs from MDD in that there is a bidirectional natnre to the mood swings and, for many patients, the rate of cycling is more rapid in BPAD than MDD. The phases of BPAD inclnde mania, hypomania, and depression, though mixed states, the simultaneous presentation of symptoms of both mania and depression, are common. 

Disorders that are characterised by changes in mood are known as affective disorders, which are depression and mania, now known as unipolar and bipolar affective disorders, respectively. Mood is considered to depend upon the concentration of an amine neurotransmitter in some parts of the brain. 

Mania, manic-depression and depression, which comprise the affective disorders, are relatively common it has been estimated that there is an incidence of at least 2% in most societies throughout the world. There is good evidence to suggest that genetic factors play a considerable role in predisposing a patient to an affective disorder. In a seminal Danish twin register study, in which the incidence of affective disorders was determined in all twins of the same sex born in Denmark between 1870 and 1920, a total of 110 pairs of twins were identified in which one or both had manic-depression. The concordance rates, that is the rate of coexistence of the disorder in twin pairs, for all types of affective disorder were found to be... 

The various hypotheses that have been advanced regarding the biochemical cause of mania mainly centre on the idea that it is due to a relative excess of noradrenaline, and possibly dopamine, with deficits also arising in the availability of 5-hydroxytryptamine (5-HT) and acetylcholine. This simplistic view forms the basis of the amine theory of affective disorders... 

Pharmacology Lithium alters sodium transport in nerve and muscle cells, and effects a shift toward intraneuronal catecholamine metabolism. The specific mechanism in mania is unknown, but it affects neurotransmitters associated with affective disorders. Its antimanic effects may be the result of increases in norepinephrine reuptake and increased serotonin receptor sensitivity. Pharmacokinetics ... 

In Prozac Diary Lauren Slater observes that though a great deal has been written about what happens to people when they become sick, very little has been said about the equally powerful consequences of becoming well. Like the inmates portrayed in the movie The Shawshank Redemption who cannot deal with freedom after decades of institutionalization, some of my interviewees found it difficult to contemplate—and sometimes live—a life free of depression or mania. They missed their illness because it is who they fundamentally define themselves to be. While the vast majority of those who suffer from affective disorders choose pills over pain, the choice is not as easy as one might imagine ... 

The accounts in this book converge on a difficult truth Except in rare instances, medications do not cure affective disorders. Mental illnesses are chronic. There is typically an unpredictable ebb and flow to emotional distress. For some, difficult episodes of depression or mania are punctuated by periods of remission. Others describe good days and bad days. Yet others muddle along in a state of unre-... 

Horrigan, J.P. and Barnhill, L.J. (1999) Guanfacine and secondary mania in children. / Affect Disord 54 309-314. 

Knoll, J., Stegman, K., and Suppes, T. (1998) Clinical experience using gabapentin adjunctively in patients with a history of mania or hypomania. Affect Disord 49 229-233. 

Geller, B., Zimerman, B., Williams, M., Bolhofner, K., Craney, J.L., DelBello, M.P., and Soutullo, C. (2001) Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. / Am Acad Child Adolesc Psychiatry 40 450-455. 

T, Vestergaard, P.A., and Carbonell, C. (2000) A review of randomized, controlled clinical trials in acute mania./ Affect Disord 59 S31-S39. 

Strober, M., DeAntonio, M., Schmidt-Lackner, S., Freeman, R., Lam-pert, C., and Diamond,/. (1998) Early childhood attention deficit hyperactivity disorder predicts poorer response to acute lithium therapy in adolescent mania. / Affect Disord 51 145-151. 

Controlled and uncontrolled or open studies of the CCBs in affective illness are reviewed in Table 6-3. Initial open and blind studies of the phenyl-alkylamine L-type CCB verapamil were positive in the affective disorders, particularly in the treatment of acute mania. However, some preliminary controlled data are negative (Janicak et al. 1998) these data are highly subject to a type II error with the design used, the relatively small numbers of patients randomly selected for verapamil and placebo, and the associated relatively high placebo response rate in acute mania observed in many controlled studies... 

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