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Geriatric bipolar disorder: Maintenance treatment and prognosis http://www.uptodate.com/contents/geriatric-bipolar-disorder-maintenan... Official reprint from UpToDate® www.uptodate.com ©2013 UpToDate® Geriatric bipolar disorder: Maintenance treatment and prognosis Authors Martha Sajatovic, MD Peijun Chen, MD, MPH, PhD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2013. | This topic last upd
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  Official reprint from UpToDatewww.uptodate.com ©2013 UpToDate Authors Martha Sajatovic, MDPeijun Chen, MD, MPH, PhD Section Editors Paul Keck, MDKenneth E Schmader, MD Deputy Editor  David Solomon, MD Geriatric bipolar disorder: Maintenance treatment and prognosisDisclosures  All topics are updated as new evidence becomes available and our peer review processis complete. Literature review current through:  Oct 2013.| This topic last updated:  Out 28, 2012. INTRODUCTION  — The clinical features and treatment of older bipolar patients differ from those of younger patients [1]. Up to 25 percent of all bipolar patients are elderly [2], and the absolute number of geriatric bipolar  patients is expected to increase as the world’s population ages over the next several decades [3,4].This topic reviews the maintenance treatment and prognosis of geriatric bipolar disorder. The epidemiology,pathogenesis, clinical features, assessment, diagnosis, and acute treatment of geriatric bipolar disorder arediscussed separately, as are the clinical features, diagnosis, acute treatment, and maintenance treatment of bipolar disorder in mixed-age patients.(See Geriatric bipolar disorder: Epidemiology, clinical features, assessment, and diagnosis .)(See Geriatric bipolar disorder: Acute treatment .)(See Bipolar disorder in adults: Epidemiology and pathogenesis .)(See Bipolar disorder in adults: Pharmacotherapy for acute mania, mixed episodes, and hypomania .)(See Bipolar disorder in adults: Pharmacotherapy for acute depression .)(See Bipolar disorder in adults: Maintenance treatment .) DEFINITIONSGeriatric bipolar disorder   — The minimum age used to define geriatric bipolar disorder is generally 60 years [5].However, some authorities use an age cut-off of 50, 55, or 65 years [6]. Geriatric bipolar disorder includes bothaging patients whose mood disorder presented earlier in life, and patients whose mood disorder presents for thefirst time in later life [1,7].Bipolar disorder is characterized by episodes of major depression (table 1), mania (table 2), and hypomania (table 3), as well as mixed episodes (major depression concurrent with mania) [8]. However, the clinical features of  bipolar disorder are different for older and younger patients in that [1,9-12]:Cognitive impairment is more common and severe in geriatric patientsComorbid general medical illnesses are more common in older patientsExcessive sexual interest and behavior during manic or hypomanic episodes appear to be less common inolder patientsComorbid anxiety and substance use disorders may be less common in geriatric patientsThe clinical features and diagnosis of geriatric bipolar disorder are discussed separately. (See Geriatric bipolar disorder: Epidemiology, clinical features, assessment, and diagnosis .) Remission  — Remission is defined as the resolution of mood symptoms, or improvement to the point that only oneor two symptoms of mild intensity persist. If psychotic features (delusions or hallucinations) are also present,resolution of the psychosis is required for remission. The rate of remission from geriatric bipolar mood episodes isdiscussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'Recovery from moodepisodes'.) TREATMENT  — Maintenance treatment is indicated for geriatric bipolar disorder because patients who remit from ®® Geriatric bipolar disorder: Maintenance treatment and prognosishttp://www.uptodate.com/contents/geriatric-bipolar-disorder-maintenan...1 de 1102/12/2013 04:45  a mood episode are at high risk for suffering another episode: A prospective study of 220 bipolar patients assessed course of illness for approximately 40 years and foundthat the median number of lifetime episodes was 10 and that the risk of recurrence remained constant up tothe age of 70 years or more [13] A retrospective study of 26 geriatric bipolar patients found that 38 percent had a lifetime history of at leastthree mood episodes [14]Multiple studies suggest that approximately 20 percent of geriatric bipolar patientswill sustain four or morerecurrences within a 12-month period [15,16]Maintenance treatment for geriatric bipolar patients is consistent with practice guidelines from the AmericanPsychiatric Association [17], National Institute for Health and Clinical Excellence [18], Canadian Network for Mood and Anxiety Treatments [19], and British Association for Psychopharmacology [20]. Pharmacotherapy  — Maintenance treatment for geriatric bipolar disorder usually includes pharmacotherapy[19,21]. Acutely ill patients who remit with a medication regimen should generally be maintained on the same drugsand doses. However, patients successfully treated withfluoxetine plusolanzapine for an episode of major  depression are generally tapered off of fluoxetine within a few months of remission.(See'Following recovery frombipolar major depression' below.)Comorbid diseases, concomitant medications, and age-related physiologic changes often alter a drug’spharmacodynamics and pharmacokinetics, which can affect therapeutic and adverse responses. Pharmacologicissues in elderly bipolar patients are discussed separately. (See Geriatric bipolar disorder: Acute treatment ,section on 'Pharmacologic issues'.) Evidence of efficacy  — Evidence for the efficacy of maintenance treatment for geriatric bipolar disorder includes subgroup analyses of older patients in randomized trials conducted with mixed-age patients (18 to 65years): A pooled analysis of two 18-month randomized trials comparedlithium,lamotrigine, and placebo in mixed-age bipolar patients who were stable for at least four weeks [22]. In the subgroup of 98 older patients, time to intervention for an emerging episode of mania, hypomania, or mixedmania was significantlylonger with lithium (modal dose 750 mg per day) than placebo [23]. Time to intervention for an emergingepisode of major depression was significantly longer with lamotrigine (modal dose 240 mg per day) thanplacebo. These results were consistent with those from the mixed-age patients. Amongolder patients,withdrawal from treatment due to side effects occurred most often with lithium, followed by lamotrigine andplacebo (29 versus 18 and 13 percent of patients). An open-label, two-year randomized maintenance trial (Bipolar Affective disorder:Lithium/AnticonvulsantEvaluation; BALANCE) compared lithium monotherapy,valproate monotherapy, and lithium plus valproate in330 bipolar mixed-age patients [24]. Lithium monotherapy and combination treatment were superior tovalproate alone, and subgroup analyses found the results did not differ significantly between older andyounger patients. Following recovery from bipolar major depression  — Acutely ill patients who remit with a medicationregimen should generally be maintained on the same drugs and doses. However, for geriatric bipolar patients withmajor depression who remit with the combination of fluoxetine andolanzapine, and then remain stable for two to six months, we suggest tapering fluoxetine by 10 mg per week until it is discontinued, and continuing olanzapine. Thereason is that maintenance antidepressants may possibly induce mania or hypomania [25,26]. If symptoms of depression recur during the taper, the dose should be titrated back up to the full dose used to initially achieveremission. If a full-blown depressive episode develops despite increasing the dose and does not improve withinfour to eight weeks, the relapse is treated as a new acute episode; acute treatment is discussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'Bipolar major depression'.)For geriatric bipolar patients with major depression who remit with the combination of fluoxetine andolanzapine and then develop manic or hypomanic symptoms during maintenance treatment, fluoxetine should be abruptly Geriatric bipolar disorder: Maintenance treatment and prognosishttp://www.uptodate.com/contents/geriatric-bipolar-disorder-maintenan...2 de 1102/12/2013 04:45  discontinued and olanzapine continued. If a full-blown manic or hypomanic episode develops despite discontinuingfluoxetine and does not improve within four to eight weeks, the relapse is treated as a new acute episode; acutetreatment is discussed separately.(See Geriatric bipolar disorder: Acute treatment , section on 'Manic,hypomanic, and mixed episodes'.) Treatment following remission with electroconvulsive therapy  — For geriatric bipolar patients who remitwith electroconvulsive therapy (ECT), we suggest maintenance treatment withlithium, based upon its efficacy inthe subgroup of older patients who participated in randomized trials with mixed-age adult bipolar patients (18 to 65years) [23,24]. However,lamotrigine is a reasonable alternative. The maintenance drug is started the day after  ECT is completed, unless the patient is suffering cognitive impairment secondary to ECT, in which casemaintenance pharmacotherapy is delayed until the impairment has dissipated. The doseand side effects of lithiumand lamotrigine are discussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'First linemedications' and Geriatric bipolar disorder: Acute treatment , section on 'Treatment resistance'.) For geriatric bipolar patients who remit with ECT and cannot tolerate maintenance treatment withlithium or lamotrigine, reasonable alternatives includearipiprazole,carbamazepine,olanzapine,quetiapine,risperidone, valproate, or ziprasidone. There is no evidence of superior efficacy among these alternatives; the choice is thus guided by side effect profiles, potential drug-drug interactions, comorbid general medical conditions, patientpreference, and cost. The dose and side effects of these alternatives are discussed separately. (See Geriatricbipolar disorder: Acute treatment , section on 'First line medications' and Geriatric bipolar disorder: Acutetreatment , section on 'Resistant patients' and Geriatric bipolar disorder: Acute treatment , section on 'Refractorypatients'.)Maintenance ECT should be offered to geriatric bipolar patients who repeatedly remitwith ECT and then relapseduring maintenance pharmacotherapy [17]. Maintenance ECT is discussed separately. (See Overview of  electroconvulsive therapy (ECT) for adults , section on 'Continuation and maintenance ECT'.) Managing intolerable side effects  — Geriatric bipolar patients who cannot tolerate maintenance treatmentwith the minimum target dose of a medication are generally switched to another medication. For patients notreceivinglithium, we and others suggest switching to lithium [1], based upon its efficacy in analyses of results from older patients who participated in randomized trials with mixed-age adult bipolar patients (18 to 65 years) [23,24].However,lamotrigine is a reasonable alternative. The failed medication is generally tapered and discontinued over one to two weeks by the same amount for each dose decrease. As an example,olanzapine 15 mg per day isdecreased by 5 mg per day, every one to three days. At the same time, lithium or lamotrigine is started andtitrated up. The dose and side effects of lithium and lamotrigine are discussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'First line medications' and Geriatric bipolar disorder: Acute treatment ,section on 'Treatment resistance'.)For remitted geriatric bipolar patients who cannot tolerate maintenance treatment with the medication that inducedremission and are also intolerant of lithium or lamotrigine, reasonable alternatives includearipiprazole, carbamazepine,olanzapine,quetiapine,risperidone,valproate, or ziprasidone. There is no evidence of superior  efficacy among these alternatives; the choice is thus guided by side effect profiles, potential drug-drug interactions,comorbid general medical conditions, patient preference, and cost. The dose and sideeffects of these alternativesare discussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'First line medications' and Geriatric bipolar disorder: Acute treatment , section on 'Resistant patients' and Geriatric bipolar disorder: Acutetreatment , section on 'Refractory patients'.)For geriatric bipolar patients who remit with a medication combination and cannot tolerate minimum target doses,we suggest tapering and discontinuing the drug that is most troublesome and continuing with the remaining drug.The failed drug is generally tapered and discontinued over one to two weeks by the same amount for each dosedecrease. At the same time, the dose of the remaining drug should be increased within the target dose range astolerated. The dose and side effects of medications are discussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'Manic, hypomanic, and mixed episodes' and Geriatric bipolar disorder: Acutetreatment , section on 'Bipolar major depression'.) Adjunctive psychotherapy  — We suggest that older bipolar patients receiving maintenance pharmacotherapyalso receive psychotherapy that focuses upon [17,27]: Geriatric bipolar disorder: Maintenance treatment and prognosishttp://www.uptodate.com/contents/geriatric-bipolar-disorder-maintenan...3 de 1102/12/2013 04:45  Managing bipolar disorder  Accepting the illness and the limitations it imposes Adhering to treatmentDetecting and reporting prodromal symptomsLimiting or eliminating use of alcoholEliminating drugs of abuse (eg, cannabis)Regulating sleepManaging interpersonal difficultiesImproving self-esteem Age-related issues (eg, changing occupational and social roles, loss of family members and friends,reduced financial resources, or decreased functioning) Although pharmacotherapy is the cornerstone of maintenance treatment for bipolar disorder, adjunctivepsychotherapy improves outcomes compared with pharmacotherapy alone in randomized trials with mixed-ageadults (18 to 65 years) [28,29]. Thus, several practice guidelines recommend adjunctive psychotherapy[17,19,20,30].Different psychotherapy options include, in order of preference [31]:PsychoeducationCognitive-behavioral therapy (CBT)Family therapyInterpersonal therapy Adjunctive maintenance psychotherapy is discussed further. (See Bipolar disorder in adults: Maintenancetreatment , section on 'Adjunctive psychotherapy'.) Adherence  — Many geriatric bipolar patients do not adhere to treatment (although their adherence generallyexceeds that of younger patients) [32]. A study of 6461 elderly bipolar patients found that 19 percent partiallyadhered to treatment and 20 percent were nonadherent, and that comorbid substance abuse was associated withnonadherence. Poor adherence probably increases the risk of recurrence, and strategies for improving adherenceare discussed separately. (See Bipolar disorder in adults: Maintenance treatment , section on 'Adherence'.) Monitoring the patient  — Remitted geriatric bipolar patients should be evaluated regularly and monitored for recurrence of manic and depressive symptoms as well as medication side effects and cognitive decline. Particular attention is given to suicidal ideation and to psychotic symptoms. Older patients often require more vigilantmonitoring than do younger patients [33].For geriatric bipolar patients who remit and remain stable, monitoring can be tapered, with progressively longer intervals between assessments. As an example, a patient who is seen every two weeks at the time of remissioncan be seen every two weeks for one to three more visits, then every month for one to three visits, and then everytwo months for one to three visits. Continuously stable patients can ultimately be seen every three to six months.More frequent visits should be scheduled for patients who develop symptoms or side effects; monitoring acutely illpatients is discussed separately. (See Geriatric bipolar disorder: Acute treatment , section on 'Generalprinciples'.) Duration and discontinuation  — Based upon clinical experience, most geriatric bipolar patients requiremaintenance treatment for many years, and some patients require it for their entire lives. However, the duration isnot established and is generally longer in patients with:Residual symptoms, particularly suicidal ideationOngoing comorbid psychopathologyPsychosocial stressors Geriatric bipolar disorder: Maintenance treatment and prognosishttp://www.uptodate.com/contents/geriatric-bipolar-disorder-maintenan...4 de 1102/12/2013 04:45
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