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Chapter: Essentials of Psychiatry: Mental Disorders Due to a General Medical Condition

Mood Disorder with Manic Features

Mood disorder due to a general medical condition with manic features is characterized by a prominent and persistently ele-vated, expansive or irritable mood which, on the basis of the his-tory, physical or laboratory examinations can be attributed to an underlying general medical condition.

Mood Disorder with Manic Features




Mood disorder due to a general medical condition with manic features is characterized by a prominent and persistently ele-vated, expansive or irritable mood which, on the basis of the his-tory, physical or laboratory examinations can be attributed to an underlying general medical condition. Other manic symptoms, such as increased energy, decreased need for sleep, hyperactivity, distractibility, pressured speech and flight of ideas, may or may not be present.


Etiology and Pathophysiology


The vast majority of cases of sustained, elevated or irritable mood occur as part of four primary disorders, namely bipolar I disorder, bipolar II disorder, cyclothymic disorder and schizoaf-fective disorder (bipolar type). Cases of elevated or irritable mood secondary to other causes (e.g., secondary to treatment with corticosteroids) are much less common. Table 33.4 lists sec-ondary causes of elevated or irritable mood, with these causes divided into categories designed to facilitate the task of differ-ential diagnosis.


In utilizing Table 33.4, the first step is to determine whether the mania could be secondary to precipitants. Sub-stance-induced mood disorder related to drugs of abuse is covered in the relevant substance-related disorders. Of the precipitating factors listed in Table 33.4, medications are the most common offenders. Before, however, attributing the mania to one of these medications, it is critical to demonstrate that the mania occurred only after initiation of that medication; ideally, one would also want to show that themania spontaneously resolved subsequent to the medication’s discontinuation. Of the medications listed, corticosteroids, such as prednisone, are likely to cause mania, with the likelihood in-creasing in direct proportion to dose: in one study (Wolkow-itz et al., 1990), 80 mg of prednisone produced mania within five days in 75% of subjects. Levodopa is the next most likely cause, and in the case of levodopa the induced mania may be so pleasurable that some patients have ended up abusing the drug (Giovannoni et al., 2000). Anabolic steroid abuse may cause an irritable mania, and such a syndrome occurring in a “bulked up” patients should prompt a search for other clinical evidence of abuse, such as gynecomastia and testicular atrophy. Closed head injury may be followed by mania either directly upon emergence from postcoma delirium, or after an interval of months. Hemodialysis may cause mania, and in one case (Jack et al., 1983) mania occurred as the presenting sign of an even-tual dialysis dementia. Encephalitis may cause mania, as, for example, in postinfectious encephalomyelitis, with the correct diagnosis eventually being suggested by more typical signs such as delirium or seizures. Encephalitis lethargica (Von Economo’s disease; European Sleeping Sickness) may also be at fault, with the diagnosis suggested by classic signs such as sleep reversal or oculomotor paralyses.


Mania occurring secondary to disease with distinctive features is immediately suggested by these features, as listed in Table 33.4. Some elaboration may be in order regarding ma-nia secondary to cerebral infarction. This cause, of course, is suggested by the sudden onset of the clinical disturbance, with the mania being accompanied by various other more or less localizing signs: what is most remarkable here is the variety of structures which, if infarcted, may be followed by mania


Thus, mania has been noted with infarction of the midbrain, thalamus (either on the right side or bilaterally, anterior limb of the internal capsule and adjacent caudate on the right, and subcortical white matter or cortical infarction on the right in the frontoparietal or temporal areas. Mania associated with epilepsy may also deserve additional comment. Ictal mania is characterized by its paroxysmal onset, over seconds and the diagnosis of postictal mania is suggested when mania oc-curs shortly after a “flurry” of grand mal or complex partial seizures.


Mania occurring as part of certain neurodegenerative or dementing diseases is suggested, in general, by a concur-rent dementia, and in most cases the mania plays only a minor role in the overall clinical pictures. Neurosyphilis, however, is an exception to this rule, for in patients with general paresis of the insane (dementia paralytica) mania may dominate the picture.


Of the miscellaneous or rare causes of mania, cerebral tumors are the most important to keep in mind, with mania be-ing noted with tumors of the midbrain, tumors compressing the hypothalamus, e.g., a craniopharyngioma or a pituitary adenoma, and tumors of the right thalamus, right cingulate gyrus or one or both frontal lobes.


Assessment and Differential Diagnosis


In most cases of mania secondary to precipitants, the cause (e.g., treatment with high dose prednisone) is fairly straightforward; in cases secondary to diseases with distinctive features or occurring as part of certain neurodegenerative or dementing diseases, the cause is generally readily discernible if the clinician is alert to the telltale distinctive features (e.g., a Cushingoid habitus) and to the presence of dementia indicat-ing one of the dementing disorders listed in Table 33.4. The miscellaneous or rare causes represent the “zebras” in the dif-ferential of secondary mania, and are generally only resorted to when other investigations prove unrewarding.



As a rule, it is very rare for mania to constitute the initial presentation of any of the disease or disorders listed in Table 33.4; thus, other evidence of their presence will become evident dur-ing the routine history and physical examination. Exceptions to the rule include neurosyphilis, vitamin B12 deficiency and Creutzfeldt–Jakob disease, however in all these cases continued observation will eventually disclose the appearance of other evi-dence suggestive of the correct diagnosis.


It must always be kept in mind that certain medications (e.g., antidepressants) may precipitate mania in patients with bi-polar disorder: in such cases, history will reveal earlier episodes of either depression, or mania, or both and such cases of mania should not be considered secondary.


Epidemiology and comorbidity


Relative to cases of primary mania (e.g., bipolar disorder), sec-ondary mania is relatively rare. In certain settings, however, sec-ondary mania may be so common as to merit a “top” position on the differential diagnosis; a prime example would be when prednisone is used in high doses, as in the treatment of multiple sclerosis or rheumatoid arthritis.




Most cases of medication-induced mania begin to clear in a mat-ter of days; for other causes, the course of the mania generally reflects the course of the underlying disease.




Treatment, if possible, is directed at the underlying cause. In cases where such etiologic treatment is not possible, or not rapidly ef-fective enough, pharmacologic measures are in order. Mood sta-bilizers, such as lithium or divalproex used in a fashion similar to that for the treatment of mania occurring in bipolar disorder, are commonly used: both lithium and divalproex are effective in the prophylaxis of mania occurring secondary to prednisone; case reports also support the use of lithium for mania secondary to zidovudine and divalproex for mania secondary to closed head injury. As between lithium and divalproex, in cases where there is a risk for seizures (e.g., head injury, encephalitis, stroke or tu-mors), divalproex clearly is preferable


In cases where emergent treatment is required, before lith-ium or divalproex could have a chance to become effective, oral or intramuscular lorazepam or haloperidol (in doses of 2 mg and 5 mg, respectively) may be utilized, again much as in the treat-ment of mania in bipolar disorder.


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