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Organic Causes of Mania

1988; Elsevier BV; Volume: 63; Issue: 9 Linguagem: Inglês

10.1016/s0025-6196(12)62694-9

1942-5546

Eric W. Larson, Elliott Richelson,

Schizophrenia research and treatment

Manic syndromes have many neurologic, toxic, and metabolic causes. It is important for clinicians to be able to distinguish these organic disorders from primary idiopathic mania (bipolar disorder). The cardinal symptom of organic mania is an abnormally and persistently elevated or irritable mood. Organic mania usually develops in patients who are older than 35 years of age, whereas bipolar disorder generally has its onset between late adolescence and age 25 years. In patients with the first episode of mania, the clinician should thoroughly elicit information about current symptoms, recent infections, use of drugs, and past or family history of psychiatric disorders. In addition, a complete medical examination, computed tomography of the head, electroencephalography, and screening for drugs and toxins should be done. Treatment of organic mania includes correcting the underlying disorder when possible. Manic syndromes have many neurologic, toxic, and metabolic causes. It is important for clinicians to be able to distinguish these organic disorders from primary idiopathic mania (bipolar disorder). The cardinal symptom of organic mania is an abnormally and persistently elevated or irritable mood. Organic mania usually develops in patients who are older than 35 years of age, whereas bipolar disorder generally has its onset between late adolescence and age 25 years. In patients with the first episode of mania, the clinician should thoroughly elicit information about current symptoms, recent infections, use of drugs, and past or family history of psychiatric disorders. In addition, a complete medical examination, computed tomography of the head, electroencephalography, and screening for drugs and toxins should be done. Treatment of organic mania includes correcting the underlying disorder when possible. Manic syndromes, a type of affective illness, are relatively common; the lifetime risk for either sex is about 1%.1Weissman MM Boyd JH Affective disorders: epidemiology.in: Kaplan HI Sadock BJ Comprehensive Textbook of Psychiatry/IV. Fourth edition. Williams & Wilkins, Baltimore1985: 764-769Google Scholar In addition, many toxic, metabolic, and neurologic disorders have been associated with mania. The practitioner should be able to distinguish these disorders from idiopathic manic-depressive illness or bipolar disorder. In this article, we review the clinical features and differential diagnosis of mania, with emphasis on current information about pathologic anatomic changes and neurochemistry. We also discuss evaluation and treatment strategies. Following standard nomenclature, we use the term "organic" to describe mania secondary to an identifiable medical condition. "Bipolar disorder" is used to describe the primary psychiatric syndrome for which an organic lesion is likely but has not yet been identified. For the purposes of this article, idiopathic bipolar disorder will be distinguished from "organic" mania. The diagnostic features of a manic episode are described in Table 1, as condensed from the Diagnostic and Statistical Manual of Mental Disorders—third edition, revised (DSM-III-R).2American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Revised third edition. American Psychiatric Association, Washington, DC1987Google Scholar The cardinal symptom is an abnormally and persistently elevated or irritable mood, and at least three of the associated symptoms or signs must accompany the mood disturbance. The pronounced increase in energy, impaired judgment, grandiosity, and flight of ideas often lead patients to sexual indiscretions, buying sprees, and foolish business dealings—events that damage relationships and careers. The mood is frequently mercurial, shifting from infectious good humor to irritability or depression, and often the patient lacks insight into the condition. The sex ratios are about equal, although affective disorders as a whole are more prevalent in women than in men.Table 1Diagnostic Criteria for Manic EpisodeModified from DSM-III-R.2American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Revised third edition. American Psychiatric Association, Washington, DC1987Google Scholar By permission of the American Psychiatric Association. A.Distinct period of abnormally and persistently elevated, expansive, or irritable moodB.Three of the following (or four, if mood is only irritable): 1.Inflated self-esteem or grandiosity2.Decreased need for sleep3.More talkative than usual or pressure to keep talking4.Flight of ideas or subjective feeling that thoughts are racing5.Easy distractibility6.Increase in activities or psychomotor agitation7.Excessive involvement in pleasurable activities despite risk of negative consequencesC.Substantial impairment in occupational, social, or interpersonal functioning (if this criterion is not present, describe episode as "hypomanic")D.No delusions or hallucinations lasting as long as 2 weeks in absence of prominent mood symptoms, and not superimposed on a psychotic disorder Open table in a new tab The diagnostic criteria for organic mood syndrome, manic type (organic mania) are summarized in Table 2. The criteria necessitate only that the patient have a prominent elevated or expansive mood and that, in other ways, the clinical manifestations resemble a manic episode, with no specific number of symptoms present. The patient must have evidence of an organic cause of the mood disturbance, and the manic symptoms must not occur exclusively during delirium. The manic signs may be the sole manifestation of the organic disorder, or they may coexist with other signs, such as cognitive impairment, hallucinations, and delusions. Some researchers3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar have questioned whether patients with a previous history of depression or mania should be excluded from this group because an organic insult may simply trigger an existing bipolar disorder. This question will remain unanswered until a biologic marker for idiopathic bipolar disorder is identified.Table 2Diagnostic Criteria for Organic Mood Syndrome (Manic Type)Modified from DSM-III-R.2American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. Revised third edition. American Psychiatric Association, Washington, DC1987Google Scholar By permission of the American Psychiatric Association. A.Prominent and persistent elevated or expansive moodB.Evidence from history, physical examination, or laboratory tests of one or more specific organic causes of the disturbanceC.Manic symptoms not occurring solely during delirium Open table in a new tab Organic lesions associated with manic syndromes involve the areas of the brain that modulate neurovegetative functions (such as sleep, appetite, libido, and energy) and emotion.4Cummings JL Organic psychoses: delusional disorders and secondary mania.Psychiatr Clin North Am. June 1986; 9: 293-311Google Scholar These areas include the limbic system, thalamus, and hypothalamus, together with their connections to the midbrain, basal ganglia, and frontal and temporal lobes.5Flor-Henry P On certain aspects of the localization of the cerebral systems regulating and determining emotion.Biol Psychiatry. 1979; 14: 677-698Google Scholar Right-sided lesions have been reported more frequently in patients with organic mania, but left-sided and diffuse lesions have also been reported.3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar In a recent study, investigators found that severity of head trauma and presence of a seizure focus (especially temporal lobe epilepsy) correlated with the development of posttraumatic mania.6Shukla S Cook BL Mukherjee S Godwin C Miller MG Mania following head trauma.Am J Psychiatry. 1987; 144: 93-96Google Scholar The aforementioned anatomic structures, however, interact in an integrated manner in the perception, internal formulation, and expression of emotion.7Ross ED Rush AJ Diagnosis and neuroanatomical correlates of depression in brain-damaged patients: implications for a neurology of depression.Arch Gen Psychiatry. 1981; 38: 1344-1354Crossref Scopus (217) Google Scholar Consequently, any focal or diffuse degenerative or irritative lesion in these areas could conceivably precipitate a manic episode. Neurochemical abnormalities associated with idiopathic bipolar disorder involve the ascending monoaminergic pathways (Fig. 1)8Andén N-E Dahlström A Fuxe K Larsson K Olson L Ungerstedt U Ascending monoamine neurons to the telencephalon and diencephalon.Acta Physiol Scand. 1966; 67: 313-326Crossref Scopus (910) Google Scholar and are likely to be involved in organic mania as well.9Green AR Costain DW Pharmacology and Biochemistry of Psychiatric Disorders. John Wiley & Sons, New York1981Google Scholar These pathways begin in the midbrain and interconnect the limbic system, basal ganglia, and cerebral hemispheres.8Andén N-E Dahlström A Fuxe K Larsson K Olson L Ungerstedt U Ascending monoamine neurons to the telencephalon and diencephalon.Acta Physiol Scand. 1966; 67: 313-326Crossref Scopus (910) Google Scholar, 10Nauta WJH Domesick VB Ramifications of the limbic system.in: Matthysse S Psychiatry and the Biology of the Human Brain. Elsevier/North-Holland, New York1981: 165-188Google Scholar Increases in the functional output of dopamine, norepinephrine, and serotonin have all been reported in patients with mania,9Green AR Costain DW Pharmacology and Biochemistry of Psychiatric Disorders. John Wiley & Sons, New York1981Google Scholar, 11Potter WZ Rudorfer MV Goodwin FK Biological findings in bipolar disorders.Psychiatry Update. 1987; 6: 32-60Google Scholar and current evidence favors a hyperadrenergic or hyperdopaminergic state.11Potter WZ Rudorfer MV Goodwin FK Biological findings in bipolar disorders.Psychiatry Update. 1987; 6: 32-60Google Scholar Mania has also been diagnosed in patients using or withdrawing from baclofen,12Arnold ES Rudd SM Kirshner H Manic psychosis following rapid withdrawal from baclofen.Am J Psychiatry. 1980; 137: 1466-1467Google Scholar, 13Wolf ME Almy G Toll M Mosnaim AD Mania associated with the use of baclofen.Biol Psychiatry. 1982; 17: 757-759Google Scholar, 14Kirubakaran V Mayfield D Rengachary S Dyskinesia and psychosis in a patient following baclofen withdrawal.Am J Psychiatry. 1984; 141: 692-693Google Scholar a structural analogue of γ-aminobutyric acid, which is a major inhibitory neurotransmitter that interacts with dopamine in the mesolimbic system. A specific neurochemical abnormality in mania remains elusive; it probably involves complex interactions among neurotransmitters or multiple abnormalities converging on a final common pathway of adrenergic or dopaminergic tracts. We conducted a MEDLINE search for all English-language references published from 1965 through 1987 in which organic or medical conditions were associated with mania. Further references dating back to 1892 were gathered from the articles cited in MEDLINE. The organic conditions listed as being associated with mania (Table 3) were compiled from cases that were judged to meet the DSM-III-R criteria for organic mood syndrome, manic type. In cases of multiple references to the same conditions or patient, the earliest or most clinically descriptive references are cited. Cases of organic mania in patients with past or family histories of psychiatric disorder are included, along with a specific notation of past or ongoing psychiatric disorder. In this review, however, we omitted cases of mania associated with tricyclic antidepressants,3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar monoamine oxidase inhibitors used as antidepressants,3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar, 15Folks D Arnold ES Pargyline-induced mania in primary affective disorder: case report.J Clin Psychiatry. 1983; 44: 25-26Google Scholar and elctroconvulsive therapy16Lewis DA Nasrallah HA Mania associated with electroconvulsive therapy.J Clin Psychiatry. 1986; 47: 366-367PubMed Google Scholar because of the clear risk of unmasking a primary bipolar illness by antidepressant therapy for unipolar depressive illness.3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google ScholarTable 3Organic Conditions Associated With ManiaNeurologic conditions Focal lesionsOther Tumors (hypothalamic, diencephalic, frontal) Posttraumatic encephalopathy Cerebrovascular lesions (temporal, hemispheric) General paresis Temporal lobe seizures Multiple sclerosis Thalamotomy Viral encephalitis Right hemispherectomy Cryptococcal meningoencephalitis Huntington's disease Pick's disease Wilson's disease Klinefelter's syndrome Postencephalitic parkinsonism Kleine-Levin syndrome Idiopathic calcification of basal gangliaSystemic conditions HyperthyroidismQ fever Hypothyroidism with starvation dietInfectious mononucleosis UremiaNiacin deficiency HemodialysisVitamin B12 deficiency Uremia with progressive dialysis dementiaCarcinoid Puerperal psychosisUse of hyperbaric chamberPostoperative excitementPremenstrual psychosisDrugs LevodopaCorticosteroids BromocriptineThyroid preparations Metoclopramide*Mania occurred in patients with histories of affective disorders. Modified from Cummings.4Baclofen CocaineBromides SympathomimeticsProcainamide IsoniazidMetrizamide ProcarbazineProcyclidine Cyclobenzaprine*Mania occurred in patients with histories of affective disorders. Modified from Cummings.4Phencyclidine Yohimbine*Mania occurred in patients with histories of affective disorders. Modified from Cummings.4Alprazolam*Mania occurred in patients with histories of affective disorders. Modified from Cummings.4 CimetidineTriazolam*Mania occurred in patients with histories of affective disorders. Modified from Cummings.4* Mania occurred in patients with histories of affective disorders. Modified from Cummings.4Cummings JL Organic psychoses: delusional disorders and secondary mania.Psychiatr Clin North Am. June 1986; 9: 293-311Google Scholar Open table in a new tab Neurologic lesions commonly reported in association with mania include tumors17Cummings JL Mendez MF Secondary mania with focal cerebrovascular lesions.Am J Psychiatry. 1984; 141: 1084-1087Google Scholar, 18Jamieson RC Wells CE Manic psychosis in a patient with multiple metastatic brain tumors.J Clin Psychiatry. 1979; 40: 280-283Google Scholar and vascular lesions19Oyewumi LK Lapierre YD Efficacy of lithium in treating mood disorder occurring after brain stem injury.Am J Psychiatry. 1981; 138: 110-112Crossref PubMed Scopus (114) Google Scholar, 20Jampala VC Abrams R Mania secondary to left and right hemisphere damage.Am J Psychiatry. 1983; 140: 1197-1199Google Scholar, 21Rosenbaum AH Barry Jr, MJ Positive therapeutic response to lithium in hypomania secondary to organic brain syndrome.Am J Psychiatry. 1975; 132: 1072-1073Google Scholar of the hypothalamus, diencephalon, and frontal cortex and temporal lobe seizures.22Flor-Henry P Lateralized temporal-limbic dysfunction and psychopathology.Ann NY Acad Sci. 1976; 280: 777-795Crossref Scopus (373) Google Scholar, 23Whitlock FA Neurologic disease (part 1).in: Symptomatic Affective Disorders. Academic Press, New York1983: 62-63Google Scholar Mania has been the initial symptom in some cases.17Cummings JL Mendez MF Secondary mania with focal cerebrovascular lesions.Am J Psychiatry. 1984; 141: 1084-1087Google Scholar Thalamotomy23Whitlock FA Neurologic disease (part 1).in: Symptomatic Affective Disorders. Academic Press, New York1983: 62-63Google Scholar and right hemispherectomy24Forrest DV Bipolar illness after right hemispherectomy: a response to lithium carbonate and carbamazepine.Arch Gen Psychiatry. 1982; 39: 817-819Crossref Scopus (32) Google Scholar have also been linked to mania, although evidence in the latter case is not as clear. Patients with Huntington's chorea,25McHugh PR Folstein MF Psychiatric syndromes of Huntington's chorea: a clinical and phenomenologic study.in: Benson DF Blumer D Psychiatric Aspects of Neurological Disease. Grune & Stratton, New York1975: 267-286Google Scholar Wilson's disease,26Pandey RS Sreenivas KN Patil NM Swamy HS Dopamine β-hydroxylase inhibition in a patient with Wilson's disease and manic symptoms.Am J Psychiatry. 1981; 138: 1628-1629Google Scholar idiopathic calcification of the basal ganglia,27Trautner RJ Cummings JL Read SL Benson DF Idiopathic basal ganglia calcification and organic mood disorder.Am J Psychiatry. 1988; 145: 350-353Google Scholar and postencephalitic parkinsonism28Bromberg W Mental states in chronic encephalitis.Psychiatr Q. 1930; 4: 537-566Crossref Scopus (9) Google Scholar have also manifested mania, and in Huntington's chorea, mania has been reported as the single initial manifestation. Other neurologic syndromes that may produce mania include posttraumatic encephalopathy,6Shukla S Cook BL Mukherjee S Godwin C Miller MG Mania following head trauma.Am J Psychiatry. 1987; 144: 93-96Google Scholar, 29Cohn CK Wright III, JR DeVaul RA Post head trauma syndrome in an adolescent treated with lithium carbonate—case report.Dis Nerv Syst. 1977; 38: 630-631Google Scholar multiple sclerosis,23Whitlock FA Neurologic disease (part 1).in: Symptomatic Affective Disorders. Academic Press, New York1983: 62-63Google Scholar, 30Kemp K Lion JR Magram G Lithium in the treatment of a manic patient with multiple sclerosis: a case report.Dis Nerv Syst. 1977; 38: 210-211Google Scholar syphilitic,31Mapelli G Bellelli T Secondary mania (letter to the editor).Arch Gen Psychiatry. 1982; 39: 743Crossref Scopus (4) Google Scholar viral,32Steinberg D Hirsch SR Marston SD Reynolds K Sutton RNP Influenza infection causing manic psychosis.Br J Psychiatry. 1972; 120: 531-535Crossref Scopus (28) Google Scholar, 33Wiesert KN Hendrie HC Secondary mania? A case report.Am J Psychiatry. 1977; 134: 929-930Google Scholar, 34Koehler K Guth W The mimicking of mania in "benign" herpes simplex encephalitis.Biol Psychiatry. 1979; 14: 405-411Google Scholar and cryptococcal35Thienhaus OJ Khosla N Meningeal cryptococcosis misdiagnosed as a manic episode.Am J Psychiatry. 1984; 141: 1459-1460Google Scholar central nervous system infections, Pick's disease,36Neumann MA Pick's disease.J Neuropathol Exp Neurol. 1949; 8: 255-282Crossref PubMed Scopus (64) Google Scholar Kleine-Levin syndrome,37Jeffries JJ Lefebvre A Depression and mania associated with Kleine-Levin-Critchley syndrome.Can Psychiatr Assoc J. 1973; 18: 439-444Google Scholar and Klinefelter's syndrome.38Cameron OG Landau SG Lithium carbonate treatment of mania associated with Klinefelter's syndrome (letter to the editor).JAMA. 1980; 243: 1712Crossref Scopus (6) Google Scholar Mania has been reported in patients with hyperthyroidism39Villani S Weitzel WD Secondary mania (letter to the editor).Arch Gen Psychiatry. 1979; 36: 1031Crossref Scopus (7) Google Scholar, 40Corn TH Checkley SA A case of recurrent mania with recurrent hyperthyroidism.Br J Psychiatry. 1983; 143: 74-76Crossref Scopus (19) Google Scholar and has been induced by starvation in a hypothyroid patient.41Zolese G Henryk-Gutt R Mania induced by biochemical imbalance resulting from low energy diet in a patient with undiagnosed myxoedema.Br Med J. 1987; 295: 1026-1027Crossref Scopus (3) Google Scholar In another case, a severely manic patient with bipolar disorder was refractory to lithium treatment until her primary hypothyroidism was diagnosed and corrected.42Balldin J Berggren U Rybo E Kjellbo H Lindstedt G Treatment-resistant mania with primary hypothyroidism: a case of recovery after levothyroxine.J Clin Psychiatry. 1987; 48: 490-491Google Scholar Hemodialysis43Cooper AJ Hypomanic psychosis precipitated by hemodialysis.Compr Psychiatry. 1967; 8: 168-174Abstract Full Text PDF Scopus (16) Google Scholar and uremia with progressive dialysis encephalopathy44Jack RA Rivers-Bulkeley NT Rabin PL Secondary mania as a presentation of progressive dialysis encephalopathy.J Nerv Ment Dis. 1983; 171: 193-195Crossref Scopus (12) Google Scholar have been reported to produce mania. Although no 20th century accounts have been reported, Osler45Osler W The Principles and Practice of Medicine. D Appleton and Company, New York1892: 738Google Scholar described uremia alone as a precipitant of mania, characterized by restlessness, talkativeness, noisiness, and sleeplessness. Q fever,46Schwartz RB Manic psychosis in connection with Q-fever.Br J Psychiatry. 1974; 124: 140-143Crossref Scopus (15) Google Scholar infectious mononucleosis,47Goldney RD Temme PB Case report: manic depressive psychosis following infectious mononucleosis.J Clin Psychiatry. 1980; 41: 322-323Google Scholar carcinoid,48Lehmann J Mental disturbances followed by stupor in a patient with carcinoidosis: recovery with tryptophan treatment.Acta Psychiatr Scand. 1966; 42: 153-161Crossref Scopus (21) Google Scholar niacin deficiency,49Spivak JL Jackson DL Pellagra: an analysis of 18 patients and a review of the literature.Johns Hopkins Med J. 1977; 140: 295-309Google Scholar vitamin B12 deficiency,50Goggans FC A case of mania secondary to vitamin B12 deficiency.Am J Psychiatry. 1984; 141: 300-301Google Scholar and even use of a hyperbaric chamber51Stoudemire A Miller J Schmitt F Logue P Shelton D Latson G Bennett P Development of an organic affective syndrome during a hyperbaric diving experiment.Am J Psychiatry. 1984; 141: 1251-1254Google Scholar have also been associated with manic symptoms. In 1934, "postoperative excitement"52Muncie W Postoperative states of excitement.Arch Neurol Psychiatry. 1934; 32: 681-703Crossref Scopus (13) Google Scholar was cited as a cause of mania, but no more recent cases have been reported. Puerperal53Brockington IF Cernik KF Schofield EM Downing AR Francis AF Keelan C Puerperal psychosis: phenomena and diagnosis.Arch Gen Psychiatry. 1981; 38: 829-833Crossref Scopus (226) Google Scholar and premenstrual psychoses54Williams EY Weekes LR Premenstrual tension associated with psychotic episodes: preliminary report.J Nerv Ment Dis. 1952; 116: 321-329Crossref Scopus (24) Google Scholar have been linked to mania, but substantiation in the latter case is less clear. Many drugs have been reported to produce mania; most of them modulate central monoaminergic metabolism. These agents include the dopamine agonists levodopa3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar and bromocriptine55Vlissides DN Gill D Castelow J Bromocriptine-induced mania? (letter to the editor).Br Med J. 1978; 1: 510Crossref Scopus (34) Google Scholar and the dopamine antagonist metoclopramide,56Ritchie KS Preskorn SH Mania induced by metoclopramide: case report.J Clin Psychiatry. 1984; 45: 180-181Google Scholar although in the last case the patient had had recurrent unipolar episodes of depression. Over-the-counter sympathomimetic agents57Waters BGH Lapierre YD Secondary mania associated with sympathomimetic drug use.Am J Psychiatry. 1981; 138: 837-838Google Scholar and cocaine58Post RM Cocaine psychoses: a continuum model.Am J Psychiatry. 1975; 132: 225-231Crossref PubMed Scopus (227) Google Scholar have been linked to florid manic psychoses. The monoamine oxidase inhibitor derivatives isoniazid59Jackson SLO Psychosis due to isoniazid.Br Med J. 1957; 2: 743-746Crossref Scopus (29) Google Scholar and procarbazine60Mann AM Hutchison JL Manic reaction associated with procarbazine hydrochloride therapy of Hodgkin's disease.Can Med Assoc J. 1967; 97: 1350-1353Google Scholar have been associated with mania in patients without histories of affective disorders. Cimetidine, a histamine H2 antagonist, has produced mania.61Hubain PP Sobolski J Mendlewicz J Cimetidine-induced mania.Neuropsychobiology. 1982; 8: 223-224Crossref Scopus (15) Google Scholar Cyclobenzaprine,62Beeber AR Manring Jr, JM Psychosis following cyclobenzaprine use.J Clin Psychiatry. 1983; 44: 151-152Google Scholar a structural analogue of amitriptyline, and yohimbine,63Price LH Charney DS Heninger GR Three cases of manic symptoms following yohimbine administration.Am J Psychiatry. 1984; 141: 1267-1268Google Scholar an α2-adrenergic antagonist, have been cited as producing mania, but these occurrences were in patients with previous manic episodes. Many other classes of drugs have induced well-documented cases of mania, including corticosteroids,3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar thyroid preparations,64Josephson AM Mackenzie TB Thyroid-induced mania in hypothyroid patients.Br J Psychiatry. 1980; 137: 222-228Crossref Scopus (55) Google Scholar bromides,65Sayed AJ Mania and bromism: a case report and a look to the future.Am J Psychiatry. 1976; 133: 228-229Google Scholar baclofen,12Arnold ES Rudd SM Kirshner H Manic psychosis following rapid withdrawal from baclofen.Am J Psychiatry. 1980; 137: 1466-1467Google Scholar, 13Wolf ME Almy G Toll M Mosnaim AD Mania associated with the use of baclofen.Biol Psychiatry. 1982; 17: 757-759Google Scholar, 14Kirubakaran V Mayfield D Rengachary S Dyskinesia and psychosis in a patient following baclofen withdrawal.Am J Psychiatry. 1984; 141: 692-693Google Scholar and procainamide.66Rice H Haltzman S Tucek C Mania associated with procainamide (letter to the editor).Am J Psychiatry. 1988; 145: 129-130Google Scholar Mania has occurred spontaneously after metrizamide myelography.67Kwentus JA Silverman JJ Sprague M Manic syndrome after metrizamide myelography.Am J Psychiatry. 1984; 141: 700-702Google Scholar The anticholinergic procyclidine68Coid J Strang J Mania secondary to procyclidine ('Kemadrin') abuse.Br J Psychiatry. 1982; 141: 81-84Crossref Scopus (23) Google Scholar and the dissociative anesthetic phencyclidine69Rosen A Case report: symptomatic mania and phencyclidine abuse.Am J Psychiatry. 1979; 136: 118-119PubMed Google Scholar have produced mania in patients with histories of poly-drug abuse but not affective illness. In five recent reports, the triazolobenzodiazepine compounds alprazolam70Arana GW Pearlman C Shader RI Alprazolam-induced mania: two clinical cases.Am J Psychiatry. 1985; 142: 368-369Google Scholar, 71Strahan A Rosenthal J Kaswan M Winston A Three case reports of acute paroxysmal excitement associated with alprazolam treatment.Am J Psychiatry. 1985; 142: 859-861Google Scholar, 72Pecknold JC Fleury D Alprazolam-induced manic episode in two patients with panic disorder.Am J Psychiatry. 1986; 143: 652-653Google Scholar, 73Goodman WK Charney DS A case of alprazolam, but not lorazepam, inducing manic symptoms.J Clin Psychiatry. 1987; 48: 117-118Google Scholar and triazolam74Weilburg JB Sachs G Falk WE Triazolam-induced brief episodes of secondary mania in a depressed patient.J Clin Psychiatry. 1987; 48: 492-493Google Scholar were associated with precipitation of mania. All patients, however, had histories of bipolar disorder, depression, or anxiety disorders, and in the case of triazolam, the manic symptoms were coincident only with the duration of action of the drug. One patient who became manic while taking alprazolam was switched to lorazepam therapy, a standard benzodiazepine, and the manic syndrome resolved.73Goodman WK Charney DS A case of alprazolam, but not lorazepam, inducing manic symptoms.J Clin Psychiatry. 1987; 48: 117-118Google Scholar In contrast to other benzodiazepines, alprazolam has been reported to have antidepressant efficacy75Feighner JP Aden GC Fabre LF Rickels K Smith WT Comparison of alprazolam, imipramine, and placebo in the treatment of depression.JAMA. 1983; 249: 3057-3064Crossref Scopus (170) Google Scholar and neurochemical similarities to antidepressants.76Sethy VH Hodges Jr, DH Role of β-adrenergic receptors in the antidepressant activity of alprazolam.Res Commun Chem Pathol Pharmacol. 1982; 36: 329-332Google Scholar It remains to be seen whether alprazolam can cause mania in a patient with no history of a psychiatric disorder. Finally, in a patient with bipolar disorder who had hydrochlorothiazide-induced lithium toxicity (serum level, 3.9 meq/liter), manic-appearing agitation occurred.77Nurnberger Jr, JI Diuretic-induced lithium toxicity presenting as mania.J Nerv Ment Dis. 1985; 173: 316-318Crossref Scopus (12) Google Scholar Had the physician not determined her serum lithium concentration, the dosage of the drug may have been increased to a fatal level. Although organic mania has been reported to be relatively rare,78Robinson RG Boston JD Starkstein SE Price TR Comparison of mania and depression after brain injury: causal factors.Am J Psychiatry. 1988; 145: 172-178Google Scholar a recent review listed 43 separate conditions or drugs associated with the onset of mania.4Cummings JL Organic psychoses: delusional disorders and secondary mania.Psychiatr Clin North Am. June 1986; 9: 293-311Google Scholar Many of these reports involved several patients. Amphetamines have been listed as mania-inducing drugs,4Cummings JL Organic psychoses: delusional disorders and secondary mania.Psychiatr Clin North Am. June 1986; 9: 293-311Google Scholar but in our review, we found references only to euphoria3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar, 79Martin WR Sloan JW Sapira JD Jasinski DR Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methyl-phenidate in man.Clin Pharmacol Ther. 1971; 12: 245-258Crossref PubMed Scopus (816) Google Scholar and toxic psychosis.79Martin WR Sloan JW Sapira JD Jasinski DR Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methyl-phenidate in man.Clin Pharmacol Ther. 1971; 12: 245-258Crossref PubMed Scopus (816) Google Scholar The antiparasitic agent niridazole has also been described as precipitating mania;80Drugs that cause psychiatric symptoms.Med Lett Drugs Ther. 1984; 26: 75-78Google Scholar however, the original references describe confusion, hallucinations, delusions, suicidal behavior, and seizures81Calloway SP Suicide and neuropsychiatric side effects in patients taking niridazole.Med J Zambia. 1976; 10: 70-73Google Scholar, 82Jordan P Preliminary observations on the use of CIBA 32644-Ba in S. mansoni at Mwanza, Tanzania.Acta Trop (Basel) [Suppl]. 1966; 9: 123-131Google Scholar but not mania. We included three drugs (metoclopramide,56Ritchie KS Preskorn SH Mania induced by metoclopramide: case report.J Clin Psychiatry. 1984; 45: 180-181Google Scholar cyclobenzaprine,62Beeber AR Manring Jr, JM Psychosis following cyclobenzaprine use.J Clin Psychiatry. 1983; 44: 151-152Google Scholar and yohimbine63Price LH Charney DS Heninger GR Three cases of manic symptoms following yohimbine administration.Am J Psychiatry. 1984; 141: 1267-1268Google Scholar) that produced mania in patients with histories of depression or mania because these drugs are not antidepressants and may pose a risk to patients taking them for nonpsychiatric reasons. Despite their similarities to antidepressants, alprazolam70Arana GW Pearlman C Shader RI Alprazolam-induced mania: two clinical cases.Am J Psychiatry. 1985; 142: 368-369Google Scholar, 71Strahan A Rosenthal J Kaswan M Winston A Three case reports of acute paroxysmal excitement associated with alprazolam treatment.Am J Psychiatry. 1985; 142: 859-861Google Scholar, 72Pecknold JC Fleury D Alprazolam-induced manic episode in two patients with panic disorder.Am J Psychiatry. 1986; 143: 652-653Google Scholar, 73Goodman WK Charney DS A case of alprazolam, but not lorazepam, inducing manic symptoms.J Clin Psychiatry. 1987; 48: 117-118Google Scholar and triazolam74Weilburg JB Sachs G Falk WE Triazolam-induced brief episodes of secondary mania in a depressed patient.J Clin Psychiatry. 1987; 48: 492-493Google Scholar are also included because they are used as sedatives and hypnotics. The number of reference citations of organic mania will probably continue to increase as clinicians become more aware of the disorder. Idiopathic bipolar disorder should be diagnosed only after all organic causes have been ruled out. This can be difficult when mania is the solitary initial symptom, as in the aforementioned cases of Huntington's chorea,25McHugh PR Folstein MF Psychiatric syndromes of Huntington's chorea: a clinical and phenomenologic study.in: Benson DF Blumer D Psychiatric Aspects of Neurological Disease. Grune & Stratton, New York1975: 267-286Google Scholar herpes simplex encephalitis,34Koehler K Guth W The mimicking of mania in "benign" herpes simplex encephalitis.Biol Psychiatry. 1979; 14: 405-411Google Scholar and cryptococcal meningoencephalitis.35Thienhaus OJ Khosla N Meningeal cryptococcosis misdiagnosed as a manic episode.Am J Psychiatry. 1984; 141: 1459-1460Google Scholar In most cases cited, however, other neurologic abnormalities (delirium, dementia, unilateral motor or sensory deficits, or cranial nerve palsies) were present as well. Anosognosia and unilateral neglect have been noted in organic mania,17Cummings JL Mendez MF Secondary mania with focal cerebrovascular lesions.Am J Psychiatry. 1984; 141: 1084-1087Google Scholar corresponding to the relative preponderance of right-sided20Jampala VC Abrams R Mania secondary to left and right hemisphere damage.Am J Psychiatry. 1983; 140: 1197-1199Google Scholar or thalamic83Watson RT Heilman KM Thalamic neglect.Neurology. 1979; 29: 690-694Crossref Google Scholar lesions. Although the dramatic nature of mania may distract the clinician, it should prompt a careful assessment for other medical problems or neurologic signs. Organic mania generally develops in patients who are older than 35 years of age,3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar whereas patients with bipolar disorder usually have their first episode between late adolescence and age 25 years.84Keller MB Differential diagnosis, natural course, and epidemiology of bipolar disorders.Psychiatry Update. 1987; 6: 10-31Google Scholar Irritability and assaultive behavior were more common than euphoria in a group of patients with posttraumatic mania,6Shukla S Cook BL Mukherjee S Godwin C Miller MG Mania following head trauma.Am J Psychiatry. 1987; 144: 93-96Google Scholar although irritability is seen in idiopathic bipolar disorder as well. The literature is divided about whether a family history of affective disorders is more common79Martin WR Sloan JW Sapira JD Jasinski DR Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methyl-phenidate in man.Clin Pharmacol Ther. 1971; 12: 245-258Crossref PubMed Scopus (816) Google Scholar, 85Starkstein SE Pearlson GD Boston J Robinson RG Mania after brain injury: a controlled study of causative factors.Arch Neurol. 1987; 44: 1069-1073Crossref Scopus (118) Google Scholar or less common3Krauthammer C Klerman GL Secondary mania: manic syndromes associated with antecedent physical illness or drugs.Arch Gen Psychiatry. 1978; 35: 1333-1339Crossref Scopus (406) Google Scholar, 6Shukla S Cook BL Mukherjee S Godwin C Miller MG Mania following head trauma.Am J Psychiatry. 1987; 144: 93-96Google Scholar in organic mania in comparison with idiopathic mania. Organic mania can be clinically identical to idiopathic bipolar disorder and may respond similarly to lithium (see subsequent material). Therefore, all patients who have first-onset mania should undergo the following assessment: (1) careful elicitation of the history regarding current medical symptoms, recent infections, use of medications or drugs of abuse, and past history and family history of psychiatric disorders; (2) complete medical examination, in conjunction with a neurologic consultation if unexplained neurologic deficits are present; (3) computed tomography of the head, electroencephalography, and determination of serum thyroxine, vitamin B12, and folate levels; and (4) screening for drugs and toxins. Additional studies should be ordered if abnormalities are found. Treatment of organic mania involves correcting the underlying disorder when possible (neurosurgical removal of tumors or hematomas, correcting metabolic abnormalities, treating infections, or removing toxins or drugs). Treatment with lithium carbonate has proved to be effective in many patients with fixed or progressive lesions (central nervous system tumors,18Jamieson RC Wells CE Manic psychosis in a patient with multiple metastatic brain tumors.J Clin Psychiatry. 1979; 40: 280-283Google Scholar strokes,19Oyewumi LK Lapierre YD Efficacy of lithium in treating mood disorder occurring after brain stem injury.Am J Psychiatry. 1981; 138: 110-112Crossref PubMed Scopus (114) Google Scholar, 20Jampala VC Abrams R Mania secondary to left and right hemisphere damage.Am J Psychiatry. 1983; 140: 1197-1199Google Scholar, 21Rosenbaum AH Barry Jr, MJ Positive therapeutic response to lithium in hypomania secondary to organic brain syndrome.Am J Psychiatry. 1975; 132: 1072-1073Google Scholar Klinefelter's syndrome,38Cameron OG Landau SG Lithium carbonate treatment of mania associated with Klinefelter's syndrome (letter to the editor).JAMA. 1980; 243: 1712Crossref Scopus (6) Google Scholar and temporal lobe epilepsy22Flor-Henry P Lateralized temporal-limbic dysfunction and psychopathology.Ann NY Acad Sci. 1976; 280: 777-795Crossref Scopus (373) Google Scholar). Carbamazepine has been successfully used in addition to lithium therapy in a patient who underwent right hemidecortication and subsequently had mania24Forrest DV Bipolar illness after right hemispherectomy: a response to lithium carbonate and carbamazepine.Arch Gen Psychiatry. 1982; 39: 817-819Crossref Scopus (32) Google Scholar and also in mania attributable to head trauma.86Stewart JT Hemsath RH Bipolar illness following traumatic brain injury: treatment with lithium and carbamazepine.J Clin Psychiatry. 1988; 49: 74-75Google Scholar We thank Carol L. Cooper for secretarial assistance.