Affective disorder

Affective disorders are a group of diseases in which there is an alteration of mood such that normal life is affected. 

Common symptoms Somatic symptoms Psychotic symptoms 

Decrease in concentration Reduced activity/agitation Hallucinations 

Decrease in self-confidence Reduced sexual activity Delusions 

Mood can be abnormally lowered, as in depression (also known as unipolar depression), abnormally elevated as in mania or an alternation of the two, as in manic-depression (also known as bipolar depression). 

Family, twin, and adoption studies have shown the effect of genetic factors in the affective disorders. Some evidence is seen of at least two distinct subgroups, one X-linked and the other transmitted on chromosome 11 (12-18). Reevaluation of the data by the original authors after additional clinical information became available has led to their modification of the conclusions (19). Clinical correlates of the genetic linkage have been reviewed recently (20, 21) and the codistribution of blood groups was also studied (22). 

Females are approximately twice as likely to suffer the disorder as males, with an increased incidence after menopause (23). Patients with recurrent affective illnesses are less likely to be married than are normal subjects, perhaps as a result of the disease, which is damaging to relationships, and there is some evidence that they tend to come from a higher socioeconomic background (24). The risk of suicide during severe depressive phases of the disease is high and, at least in the lower age groups, this is a major cause of death. 

In some patients the cyclical nature of the illness is particularly apparent and is characterized by regular, very rapid fluctuations in mood, and we have reported some interesting case histories in which these cycles were accurately recorded over long periods (23, 25). 

Lithium was introduced by Cade in 1949 for the treatment of acute mania (30). Unfortunately, the serious toxic effects of lithium were first recognized quite independently at about the same time, when lithium salts were used as a substitute for table salt in treatment of hypertension in the United States. Use of Westral, a lithium-containing salt substitute, caused a number of deaths (31,32). This unfortunate coincidence delayed the acceptance of lithium in psychiatry until Schou and others showed that lithium could safely be used in manic depressive disorder at rather lower doses than those used by Cade (33). The therapeutic index, however, is low. After its reluctant acceptance, the spectrum of therapeutic activity claimed for lithium then widened for a time, to include a broad range of psychiatric disorders, including schizophrenia. 

Lithium is administered orally, usually as lithium carbonate in tablet form at a total dose of up to 30 mmol (2 g) per day. Treatment is monitored using regular estimations of blood lithium, taken 12 hr after the previous dose (40, 41). These serum lithium concentrations should lie in the range 0.4-0.8 mM, and higher levels may be associated with toxic side effects, which can include tremor, dizziness, drowsiness, and diarrhea (42, 43). 

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Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

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. 

VMATs are irreversibly inhibited by the potent antihypertensive drug reserpine. The depressive effects of reserpine helped to formulate the original monoamine hypothesis of affective disorders. Reseipine also appears to interact with the transporters near the site of substrate recognition. Tetrabenazine, which is used in treatment of movement disorders, inhibits VMAT2 much more potently than VMAT1, consistent with the less hypotensive action of this agent. 

Lynskey MT The comorbidity of alcohol dependence and affective disorders treatment implications. Drug Alcohol Depend 52 201-209, 1998... 

Dean AJ, Bell J, Mascord DJ, et al A randomized, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms. J Affect Disord 72 ... 

Nunes EV, Quitkin EM, Brady R, et al Imipramine treatment of methadone maintenance patients with affective disorder and illicit drug use. Am J Psychiatry 148 667-669, 1991... 

Forder J, Kavanagh S, Fenyo A (1996). A comparison of the cost-effectiveness of sertraline versus tricyclic antidepressants in primary C2src. J Affective Disord 58y 97—111. 

The anxiety disorders are a case in point. They comprise a range of conditions contiguous with the affective disorders and the stress responses (Table 4.1). Much overlap and comorbidity exist. Furthermore, definitions and diagnostic criteria have changed substantially over the years. For example, generalized anxiety disorder is a rare condition in its pure form, but a common condition if comorbid phobic and depressive disorders are accepted. 

Further detailed analyses of the ECA data have been extrapolated to USA national costs (Rice and Miller, 1998). It was calculated that the economic costs of mental disorders in 1990 in the USA totalled US 147.8 billion. Anxiety disorders were the most cosdy, amounting to 46.6 billion, just under a third of the total. Direct costs spent on mental health care totalled 67 billion, of which anxiety disorders accounted for only 11 billion (16.5%). Drug costs were 2191 million, of which anxiety disorders accounted for 1167 million—over half Morbidity costs—the value of goods and services not produced because of mental disorders — amounted to 63.1 billion, with anxiety disorders accounting for 34.2 billion, 54.2% of the total. This reflects the high prevalence of anxiety disorders in the community and the high associated rate of lost productivity. In contrast, patients with affective disorders appeared better able to function (Rice and Miller, 1995). In summary, anxiety disorders are common, disruptive and costly to society drug treatment is a substantial element of treatment costs (11%) compared with, say, schizophrenia (2.2%). 

The usually accepted prevalences for generalized anxiety disorder (GAD) are around 1.6% for current, 3.1% for 1 year and 5.1% lifetime (Roy-Byrne, 1996). The condition is twice as common in women as in men (Pigott, 1999). A small minority (10%) have GAD alone, and about the same proportion suffer from mixed anxiety and depression. Morbidity is high. About a half of those with uncomplicated GAD seek professional help, but two-thirds of those with comorbid GAD do so. Up to a half take medication at some point. The condition may coexist with other anxiety disorders such as phobias, with affective disorders, or with medical conditions such as unexplained chest pain and irritable bowel syndrome. 

Rice DP, Miller LS (1995). The economic burden of affective disorders. Br JPsychiatry 166 (suppl. 27), 34-42. 

Few papers have looked at the economic implications of bipolar affective disorder. Most of the published studies look at direct medical costs over the course of a year. Industry-sponsored studies focus on the benefits of a new treatment over older treatments. However, factors individual to a particular patient are likely to be more important than the average cost of a particular treatment. These include selection of patients who are likely to respond to a particular treatment, and psychoeducation coupled with encouragement during follow-up and carefial monitoring, to avoid such expensive outcomes as ftill-blown relapse, serious toxicity or suicide. 

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. 

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... 

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