Metabolic disorder

Mr. D is a 69-year-old married man who comes to your office with his wife. His wife tells you that he has become more irritable and hyperverbal, with decreased need for sleep. He also has been on several trips to a local casino where he has lost significant sums of money. He has been more sexually preoccupied, according to his wife, who is quite distressed by these behavioral changes. His medications include lisinopril, 30 mg/d, and nortriptyline, 50 mg/d.

Mr. D's past medical history is significant only for hypertension. He first had an episode of severe depression at age 45 for which he was hospitalized. That was followed by two subsequent episodes in which he was managed as an outpatient with antidepressants and psychotherapy. He has no history of suicide attempts or assaultive behaviors. He drinks a glass of wine with dinner most evenings. He has no other substance abuse history and does not smoke.

On examination in your office, Mr. D is mildly disheveled, his speech is pressured, and he assures you, loudly at times, that he is "quite fine." He appears irritable, particularly with his wife, as she provides collateral information. He has difficulty sitting still during the interview, preferring to walk about your office examining your artwork. His thoughts appear to fly from one subject to another and he is quite distractible. Mr. D boasts quite proudly to you of his sexual prowess and his success at blackjack. He is alert and fully oriented. He has no insight into this recent change in his behavior and says he cannot understand why other people cannot see that he is just enjoying his retirement.

You obtain permission to talk to his psychiatrist and, after a telephone consultation, you decide to stop his nortriptyline. Although you were aware of this patient's previous diagnosis of recurrent depressions, his psychiatrist is concerned that he is now experiencing a manic episode. He reminds you that a manic episode includes:

1. A distinct period of at least 1 week (less if hospitalized) of abnormal elevated mood (may be irritable or expansive)

2. Three or more of the following symptoms have been present to a significant degree:

a) Grandiosity or increased self-esteem

b) Decreased need for sleep

c) Pressured speech

d) Racing thoughts or flight of ideas

e) Easily distractible

f) Psychomotor agitation or increased goal-directed activity

g) Excessive involvement in activities that appear pleasurable but may have painful consequences (eg, gambling or sexual indiscretions).

These symptoms, which are not caused by any other medical condition or illicit substance, have caused significant impairment in the patient's level of functioning. Individuals who have had one or more episodes of major depression and have had at least one manic or mixed episode meet the criteria for a diagnosis of Bipolar I disorder. Individuals with Bipolar II disorder have had at least one major depressive episode and at least one hypomanic episode but never actually had a manic or mixed episode (Adapted from DSM-IV).

You agree with the psychiatrist that Mr. D indeed seems to be experiencing a manic episode and you talk to him and his wife. He agrees to a trial of lithium, which you start at 150 mg/bid increasing to 300 mg/bid after 2 days when he returns for a follow-up. You also give him clonazepam, 0.5 mg/bid, and 1 mg/qhs for sleep. You book an outpatient MRI of his brain and arrange for lab work. You advise his wife to bring him back to your office or to the nearest ER, should his symptoms change or his behavior deteriorate further with aggressive actions or suicidal thoughts, which would necessitate hospitalization for further stabilization. His laboratory work and MRI scan are normal. He is encouraged also to follow up with his outpatient psychiatrist to continue therapy. After about 10 days, his wife reports that he is doing much better, and after 6 weeks he appears to be at baseline.

Bipolar disorder in later life

Bipolar disorder is a chronic psychiatric disorder characterized by at least one manic or hypomanic episode and depression during a person's lifetime. It is associated with increased use of mental health services, (1) disability, poorer quality of life, and increased mortality from co-morbid medical conditions (2,3) and suicide.

Because large community-based epidemiologic studies are few in number, the overall incidence and prevalence of bipolar disorders in older persons is difficult to estimate. It may account for up to approximately 20% of the mood disorder presentations seen in older persons. (4) New onset mania in later life is more rare, with a reported prevalence rate of less than 1%, (5) with men appearing to be at higher risk than women. (6)

In general, older persons who present with new onset manic symptoms (or "secondary mania" (7)) usually have an underlying medical or neurologic disorder. Such conditions include hyperthyroidism, cardiovascular disease, infection, metabolic disturbances, strokes (particularly those involving the right orbitofrontal and basotemporal areas), brain tumors, and medication-induced (eg, steroids).

These individuals with new onset mania have fewer family members with mood disorders and have a much higher mortality rate (non-specific causes) compared with older persons with depression. Mania in older persons may present with delirious symptoms, such as disorientation, confusion, and perceptual abnormalities. (8) Mania can be induced for the first time when treated with antidepressants for depression, particularly with tricyclic antidepressants (9) or during the withdrawal of these medications. (10)

Another subgroup may present with repeated episodes of depression starting in middle age, which then convert to manic episodes about 15 years later. This group has a higher rate of affective disorders in their first-degree relatives. (11) Mania may also occur in schizoaffective disorder, but this is less frequently diagnosed in older persons. Older patients who present with depression may be bipolar, and a careful history of possible past hypomanic/manic episodes may help clarify this.

The recommended workup of these mania patients includes a careful history, paying particular attention to prescribed, over-the-counter, and herbal medications and dietary supplements, physical examination, laboratory testing, and selected imaging investigations. History taking should focus on any previous episodes of depression, mania, and hypomania, including post-partum episodes as well as previous suicide attempts and family history of psychiatric disorders. Laboratory tests include serum chemistries (sodium, potassium, BUN, creatinine), complete blood count, and thyroid function tests (include TSH, T3RIA, and T4). Brain imaging is advised (CT or MRI), particularly if there is a new onset of symptoms or focal findings on examination. Other tests to consider based upon the history include tests for HIV and syphilis.

Care of patients with secondary mania requires close collaboration between the primary care physician, the psychiatrist, and family members or other caregivers. Patients may need an inpatient stay to complete a comprehensive workup, to carefully initiate treatment, or if they are manic, severely depressed, or suicidal. Family members may help persuade a patient to agree to an inpatient stay but involuntary commitment may have to be considered if the patient is suicidal, manic, or severely depressed and debilitated. Psychosocial interventions may benefit patients and their caregivers. It has been reported that patients with bipolar disorder and lower levels of social support may be more likely to experience treatment resistance and even increased lengths of hospital stay. (12) As persons with this disorder age, the episodes may become longer in duration and harder to treat.

Pharmacologic treatments

Treatment of acute mania in older persons is similar to what is used in younger adults, but using lower starting doses and slower titration schedules. Antidepressant agents should be tapered and stopped if the patient is manic. The mood stabilizing medications used to treat manias include: lithium (see table for key points), divalproate (check platelets and liver function tests regularly), and carbamazepine (obtain baseline ECG and check CBCs regularly as carbamazepine may cause leukopenia and, more rarely, agranulocytosis). Lithium may be less efficacious in mania secondary to medical or neurologic disorders. Adjunctive agents may include lamotrigine, gabapentin, (13) or benzodiazepines (clonazepam or lorazepam). Benzodiazepines may be useful in the treatment of agitation either alone or in combination with antipsychotic agents. Aim to taper and discontinue benzodiazepines and neuroleptics after patient is in remission. Anticonvulsants may be responsible for approximately 10% of adverse drug reactions in older adults and this number may be further increased in nursing home populations. (14) (See Table 2 on www.geri.com for details.)

The atypical antipsychotics, such as olanzepine, risperidone, and quetiapine, may also be used to treat psychotic symptoms, but large randomized trials have not been reported as yet for this older, bipolar patient population. (15)

If patients also have diabetes, obesity, or hyperlipidemia, then olanzapine, clozapine, and lower potency antipsychotics should probably be avoided.

* Quetiapine is the first choice for patients with Parkinson's disease.

* Patients with QTC prolongation or cardiac failure should avoid zisprasidone, clozapine, as well as low- to mid-potency antipsychotics, such as thioridazine or pimozide.

* Risperidone or quetiapine may be more suitable for patients with constipation, diabetes, hyperlipidemia, cognitive impairment, and dry eyes or mouth. (16)

* The older, more potent agents, such as haldol, may induce extrapyramidal side effects, which may impair the individual's mobility and level of functioning.

Efforts should be made to limit the length of treatment with antipsychotic agents in view of their side effects.

Other treatments that may be considered include electroconvulsive therapy (for either medication refractory mania or depression, or for those who cannot tolerate medications). Care should be taken when prescribing antidepressants, particularly monoamine oxidase inhibitors, TCA's, nefazadone, and the more potent inhibitors of the cytochrome P450 enzymes, fluoxetine, fluvoxamine, and paroxetine.

Conclusion

Your patient's pressured speech, decreased need for sleep, poor judgment with increased spending, and sexual preoccupation were all suggestive of bipolar disease. The medical evaluation was negative for general medical conditions that may have contributed to the manic presentation. The patient was stabilized on lithium citrate, and he agreed to continue follow-up with a community psychiatrist.

References

(1.) Bartels SJ, Forester B, Miles KM, Joyce T. Mental health service use by elderly patients with bipolar disorder and unipolar major depression. Am J Geriatr Psychiatry 2000; 8(2):160-6.

(2.) Dhingra U, Rabins PV. Mania in the elderly: A 5 to 7 year follow-up. J Am Geriatr Soc 1991; 39(6):581-3.

(3.) Shulman KI, Tohen M. Unipolar mania reconsidered: Evidence from an elderly cohort. Br J Psychiatry 1994; 164(4): 547-9.

(4.) Young RC. Bipolar mood disorders in the elderly. Psychiatr Clin North Am 1997; 20(1):121-36.

(5.) Young RC, Klerman GL. Mania in late life: Focus on age at onset. Am J Psychiatry 1992; 149(7):867-76.

(6.) McDonald, WM, Wermager J. Pharmacologic treatment of geriatric mania. Curr Psychiatry Rep 2002; 4(1): 43-50.

(7.) Shulman KI, Tohen M, Satlin A, Mallya G, Kalunian D. Mania compared with unipolar depression in old age. Am J Psychiatry 1992; 149(3):341-5.

(8.) Weintraub D, Lippmann S. Delirious mania in the elderly. Int J Geriatr Psychiatry 2001; 16(4):374-7.

(9.) Young RC, Jain H, Kiosses DN, Meyers BS. Antidepressant-associated mania in late life. Int J Geriatr Psychiatry 2003; 18(5):421-4.

(10.) Ali S. and Milev R. Switch to mania upon discontinuation of antidepressants in patients with mood disorders: A review of the literature. Can J Psychiatry 2003; 48(4):258-64.

(11.) Stone K. Mania in the elderly. Br J Psychiatry 1989; 155:220-4.

(12.) Beyer J L, Kuchibhatla M, Looney C, Engstrom E, Cassidy F, Krishnan KR. Social support in elderly patients with bipolar disorder. Bipolar Disord 2003; 5(1):22-7.

(13.) Sethi MA, Mehta R, Devanand DP. Gabapentin in geriatric mania. J Geriatr Psychiatry Neurol 2003; 16(2):117-20.

(14.) Lackner TE. Strategies for optimizing antiepileptic drug therapy in elderly people. Pharmacotherapy 2002; 22(3): 329-64.

(15.) McDonald WM. Epidemiology, etiology, and treatment of geriatric mania. J Clin Psychiatry 2000; 61 Supp 13:3-11.

(16.) Alexopoulos GS, Streim J, Carpenter D, Docherty JP; Expert Consensus Panel for Using Antipsychotic Drugs in Older Patients. Using antipsychotic agents in older patients. J Clin Psychiatry 2004; 65 Suppl 2:5-102.

RELATED ARTICLE: Table Lithium use in older adults: key points.

Dosing

Start with low doses and titrate slowly as patients may become toxic at lower levels. Steady state achieved after 5 days. Draw blood levels 8-12 hours after previous dose. Check levels every 6 months as an outpatient but sooner if you suspect any signs of toxicity or renal impairment.

Hemodialysis patients should receive dose after dialysis.

If renal impairment is present and GFR is 10-50 mL/min give 50-75% of the usual dose; if GFR is less than 10 mL/min then give 50% of the usual dose.

Contraindications

Severe debilitation, dehydration or sodium depletion, significant renal or cardiovascular disease.

Precautions

If debilitated, during ECT, or if protracted diarrhea, sweating, fever, and infection.

Significant cardiac disease, organic brain damage, restricted sodium intake or during diuretic therapy. Maintain daily fluid intake 2,500-3,000 mL, normal diet and salt intake.

Adverse effects

Common:

Albuminuria, oliguria, polyuria, and glycosuria. Ataxia, fine hand tremor, muscle hyperirritability, hyperactive deep tendon reflexes, blurred vision, transient scotoma. Drowsiness, muscle weakness, diarrhea, vomiting (may be sign of toxicity). Dry mouth, mild nausea, polyuria, and mild thirst. ECG changes include reversible flattening or inversion of t waves.

Serious:

Ataxia, giddiness, blurred vision, tinnitus (may be a sign of serious toxicity).

Arrhythmias, hypotension, sinus node dysfunction with severe bradycardia. Seizures and coma. Large volume of dilute urine produced (may be sign of serious toxicity) and signs of pseudotumor cerebri.

Some drug interactions

Agents that may increase lithium levels and lead to toxicity include: acetazolamide, ACE inhibitors, celecoxib, ethacrynic acid, ibuprofen, NSAIDS, mazindol, metronidazole, phenylbutazone, phenytoin, thiazide diuretics, tetracycline.

Agents that may decrease lithium levels include: calcitonin, caffeine, psyllium, sodium bicarbonate, and theophylline.

Other interactions

Carbamazepine may cause additive neurotoxicity without alteration in serum levels.

Dehydroepiandrosterone reported to cause mania.

Calcium channel blockers may exacerbate manic symptoms or cause neurotoxicity.

Combined treatment with dopamine antagonists may lead to extrapyramidal symptoms,

dyskinesia, and encephalopathic symptoms.

Levofloxacin reported to cause a synergistic reaction causing acute renal failure.

Methyldopa may increase risk of toxicity.

Avoid with phenelzine, which may cause fatal malignant hyperthermia.

Avoid potassium iodide, which may increase risk of hypothyroidism.

Avoid selective serotonin re-uptake inhibitors, which may increase the risk of serotonin syndrome.

Source: Created for Geriatrics by Jennifer Hoblyn, MB, MRCPsych, MPH.

Jennifer Hoblyn is attending geriatric psychiatrist, VA Palo Alto Health Care System, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.

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