PSYCHIATRIC POTPOURRI
| BEHAVIORAL AND MOOD DISORDERS IN PARKINSON’S DISEASE —Jennifer S. Hui, MD, Instructor of Clinical Neurology, Division of Movement Disorders, Keck School of Medicine, University of Southern California, Los Angeles |
Depression | Risk factors: study—major depression associated with cognitive impairment defined by Mini Mental State Examination (MMSE) score <24 and presence of thought disorder (eg, vivid dreams, psychosis); mild depression associated with impairment in activities of daily living, more severe extrapyramidal disease, and younger age at presentation |
| Pathophysiology: speculated to be related to neurochemical changes intrinsic to Parkinson’s disease (PD); dopaminergic pathways—dopaminergic mesocortical projections from ventral tegmental area (VTA) disrupted in patients with depression; patients with PD who have greater VTA disruption more likely to have depression; serotonergic pathways— patients with depression and PD shown to have increased cell loss in dorsal raphe nuclei; in addition, serotonin receptor binding sites decreased in raphe nuclei, frontal cortex, and basal ganglia in patients with PD, with lowest binding rates in patients with depression and PD |
| Treatment: Movement Disorders Society review—nortriptyline likely efficacious; insufficient evidence for monoamine oxidase inhibitors, paroxetine, and electroconvulsive therapy |
Psychosis | Epidemiology: more common in patients with PD and cognitive impairment and dementia, and those treated with polypharmacy, in particular, dopamine agonists and anticholinergic medications |
| Hallucinations: usually visual, vivid, but nonthreatening, and occur in context of clear sensorium, with or without preserved insight; may be induced or exacerbated by all dopaminergic medications (dopamine agonists more prone to induce psychosis, compared to levodopa; anticholinergic drugs may lead to more delirium-like state); auditory—less common; prevalence 8% to 10%; usually consist of nonthreatening neutral voices or background noise, eg, radio; tactile, gustatory, and olfactory— rare |
| Delusions: study—overall prevalence 15%; threefold higher prevalence in patients with PD and dementia; include paranoid ideations, phantom boarder, television characters in room, and spousal infidelity |
| Risk factors: increasing age; cognitive impairment; sleep disturbances; behavior disorder; duration and severity of extrapyramidal disease; no definite correlation between psychotic symptoms and increased dose and duration of dopaminergic medications |
| Pathophysiology: theory 1—dopamine receptor supersensitivity in mesolimbic system; theory 2—disruption in cholinergic pathways, leading to disruption in reticular activating system in midbrain interpeduncular nucleus |
| Treatment: Movement Disorders Society review—2 trials support use of clozapine for treatment of psychosis in patients with PD; clozapine carries black box warning for idiosyncratic agranulocytosis; in one trial, olanzapine exacerbated symptoms; quetiapine frequently used, but not supported by trial data |
Impulse Control Behaviors | Epidemiology: appear more prevalent with dopamine agonists; prevalence of pathologic gambling 0.05% to 4.8%; in recent study, prevalence of addictive behavior toward dopaminergic medications 3.4% |
| Pathophysiology: likely involves dopaminergic human reward system, in particular, mesolimbic system that underlies subjective feelings of pleasure and reward; mesolimbic system starts from VTA in midbrain, with mesolimbic fibers projecting to nucleus accumbens; cells in VTA shown to be lost in patients with PD, possibly resulting in dopamine receptor supersensitivity in nucleus accumbens and increased susceptibility to inadvertent stimulation by exogenous dopaminergic medications; dopamine levels in nucleus accumbens and prefrontal cortex elevated in drug addiction, potentially analogous to exogenous stimulation of nucleus accumbens by dopamine agonists |
| Treatment: no uniform treatment; speaker has achieved relative success by substituting dopamine agonist therapy with levodopa for treatment of worsening motor symptoms; quetiapine useful in reducing associated urges and anxiety |
| COGNITIVE BEHAVIORAL THERAPY (CBT) WITH OLDER ADULTS —Julie Loebach Wetherell, PhD, Assistant Professor of Psychiatry, University of California, San Diego, School of Medicine, La Jolla |
| Behavioral strategies: pleasant activities—“move your feet and your mood will follow”; relaxation exercises— deep diaphragmatic breathing; progressive muscle relaxation; imagery; exposure therapy—flooding; systematic desensitization; has strongest empirical evidence for treatment of several anxiety disorders; problem solving—especially useful for older adults, who may have executive functioning deficits or display procrastinating or impulsive behaviors; speaker employs SOLVE strategy (select specific problem, outline all possible solutions, list advantages and disadvantages of 2 best solutions, visualize best solution, evaluate and execute); thought stopping—helpful for people with long- term, unproductive, repetitive worry |
| Cognitive strategies: identify negative thoughts; examine evidence for and against; perform experiments, eg, deliberately making mistakes to see what happens; cost-benefit analysis, eg, retired person analyzing cost and benefit of believing self-worth connected to economic productivity |
| Modifications for older people: clarify roles and address misconceptions about therapy; accommodate sensory deficits (eg, large font sizes, bright lights, speak clearly), physical constraints (ensure offices accessible), and cognitive changes (present material verbally, visually, orally, in writing); conduct sessions at slower pace; reduce intensity of exposure therapy; study showed CBT incorporating telephone contact significantly more effective than standard treatment; house calls may be required for patients who have difficulty attending clinic; enlist family and staff |
| Learning enhancements: repetition and review; multiple modalities; mnemonics; brief informal quizzes; handouts; session recordings; homework assignments |
| Efficacy: Pinquart and Sörensen meta-analysis—CBT effective size 0.64; supportive therapy effective size 0.41 (difference not statistically significant); Wilson et al—selective serotonin reuptake inhibitors (SSRIs) slightly more effective than tricyclic antidepressants; suggests CBT and SSRIs both effective; expert consensus panel for treatment of depression in elderly—recommends combination of medication and psychotherapy; speaker’s study—CBT compared to randomized prospective trial of SSRI (citalopram) for generalized anxiety disorder (GAD); effect sizes comparable immediately after treatment |
| Functional Adaptive Skills Training (FAST) program: teaches communication skills, medication management, money management, transportation, and basic living skills for middle-aged and older patients with schizophrenia; pilot study comparing FAST to psychotropic medication found FAST participants did better than treatment-as-usual participants on performance-based measure of living skills |
| Cognitive Behavioral Social Skills Training (CBSST) study: 76 older patients with psychosis randomized to treatment as usual (pharmacotherapy) or treatment as usual plus CBSST; CBSST attempted to increase cognitive insight and ability to affect mood by changing way of thinking; also contained strategies to help identify signs and symptoms of relapse, and identify and work with support people in social environment; at 24 wk, CBSST led to significant gains on measures of insight and ability to learn material; no differences on measures of positive or negative symptoms; no significant differences in depression symptoms; patients receiving CBSST had significant improvements on the Independent Living Skills Survey (ILSS); at 12-mo follow-up, gains from CBSST had diminished but still significantly better (booster sessions may be necessary) |
| Dialectical Behavior Therapy (DBT): developed particularly for patients with borderline personality disorder who engage in parasuicidal behavior; study—group of 34 older adults with depression and comorbid personality disorders who had 8-wk trial of SSRIs without resolution of symptoms randomized to increased medication or increased medication plus DBT; DBT consisted of group skills training and individual telephone coaching to develop relationship building and repair skills; remission defined as Hamilton depression score ≤7; >70% of medication plus DBT group achieved remission immediately after treatment, compared to 47% of medication-only group; at 6-mo follow-up, 75% of DBT group asymptomatic, compared to 30% of medication-only group |
| Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) trial: incorporated depression care manager who could prescribe medications and perform problem-solving therapy; 1900 primary care patients >60 yr of age with depression or dysthymia followed for 2 yr; IMPACT intervention associated with significant improvement on 20-item Hopkins Symptom Checklist (SCL-20) depression score at 12-mo follow-up |
| Case management and CBT: in 70 patients >65 yr of age (75% people of color, and all at or below poverty line) with major depression, CBT alone had no effect on depression symptoms at 12 mo; case management alone as effective as case management plus CBT in reducing symptoms at 6 mo; at 12 mo, case management plus CBT significantly more effective than case management alone |
| Controlling Anxiety in Later-life Medical Patients (CALM) study: of 14 primary care patients enrolled in study, 13 met criteria for GAD; patients offered either 12 individual therapy sessions or treatment as usual; patients followed for 1 yr after treatment; intervention modular in design, providing targeted treatment; in pilot subjects, intervention led to dramatic decreases in scores on GAD and worry questionnaire |
| PSYCHIATRIC CONDITIONS CAUSED BY NONPSYCHIATRIC MEDICATIONS —Andrew Israel, MD, Clinical Professor of Medicine, University of California, San Diego, School of Medicine, La Jolla |
| Scope of problem: seniors represent 16% to 20% of US population and consume 40% of drugs; one third of seniors take ≥5 drugs per year; 20% take 7 drugs per year; average senior gets 15 prescriptions per year |
| Inappropriate prescribing: Curtis, 2004—study of 800,000 patients >65 yr of age (median age 73.3 yr); >20% received ≥1 drug(s) of concern according to Beer’s Criteria (one fifth received amitriptyline or doxepin); 45% of drugs had potential for serious side effects |
| Common drugs causing difficult problems: HMG-CoA reductase inhibitors—anxiety; depression; obsessions; memory loss; nonsteroidal anti-inflammatory drugs (NSAIDs)—depression; paranoia; psychosis; sulfonamides— confusion; disorientation; euphoria; calcium channel blockers—depression; fluoroquinolones—Tourette-like syndrome; paranoia; hallucinations |
| Drugs that can cause depression: antibiotics—metronidazole (Flagyl); isoniazid (INH); cycloserine (Seromycin); steroids—cortisone; methylprednisolone (Medrol); H2 blockers—cimetidine (Tagamet); ranitidine (Zantac); ophthalmic—many ophthalmic drops are β-blockers for treatment of glaucoma; systemic effects in older patients can be extreme; cardiovascular drugs—antiarrhythmics; β-blockers; diuretics (particularly those containing reserpine); central nervous system (CNS) drugs—antidepressants (some seniors prescribed bupropion in form of Zyban for smoking cessation); tranquilizers; analgesics (including over-the-counter medications); disulfiram (Antabuse) |
| Drugs that can cause psychosis: antibiotics; corticosteroids (oral and inhaled); antihistamines—diphenhydramine (Benadryl, Tylenol PM); triprolidine (Actifed); chlorpheniramine (Chlor-Trimeton); cardiovascular drugs—glycosides; antiarrhythmics (remain in tissue for long time and most cross blood-brain barrier); CNS drugs—antidepressants; tranquilizers; anticonvulsants; antiparkinsonian drugs (important to ask older patients with neurologic conditions about all drug regimens); analgesics; chemotherapy agents; thyroid agents |
| Drugs that can cause confusion and delirium: affect brain metabolism; drugs such as insulin and oral hypoglycemics should be considered; antibiotics—ciprofloxacin (Cipro); ofloxacin (Floxin); amantadine (Symmetrel); steroids—steroid psychosis well known; antihistamines—over-the-counter and prescription drugs; patients will not necessarily say they are taking them, so important to ask; hypoglycemic agents—cyclic behaviors that tend to occur at certain times of day, particularly times when patient has not eaten, suggest medication may be causing psychiatric symptoms; cardiovascular drugs—α-blockers, particularly clonidine (Catapres); gastrointestinal (GI) drugs—affect nerve junctions, particularly antispasmodics; CNS drugs—antidepressants; antipsychotics; tranquilizers; anticonvulsants; antiparkinsonian drugs |
| Drugs that can cause dementia: important to understand common drugs can cause memory loss and confusion; GI drugs—H2 blockers; cardiovascular drugs— β-blockers (considered below standard of care to allow patient to leave hospital after heart attack without β-blocker); diuretics; CNS drugs—hypnotics (daytime effects may be due to slow metabolism of hypnotics taken in the morning) |
| Drugs that can cause insomnia: anti-infectives; cold preparations; GI drugs; cardiovascular drugs; any drug that crosses blood-brain barrier and causes brain stimulation will interfere with sleep and daytime alertness |
| Diagnosis of medication-induced psychiatric disease: information commonly found in desk reference manual; ask patient to put all medications in bag and bring to next appointment; provides information on how many pharmacies being used, how many physicians have prescribed drugs, and how many medicines prescribed long time ago still being taken; dispose of expired and unused drugs for patient; talk to family members; utilize pharmacy databases to determine medications being used; subtraction of medications often works better than adding new ones; do not let pharmacies, health plans, or others substitute drugs without consent; obligation is on physician to ensure substitute drug has same actions; take careful history of when drugs started and when doses changed to determine whether drug interactions occuring |
Educational Objectives
| The goal of this program is to provide the listener with information on behavioral and mood disorders in Parkinson’s disease (PD), cognitive behavioral therapy (CBT) for older patients, and psychiatric conditions caused by nonpsychiatric medications. After hearing and assimilating this program, the clinician will be better able to: |
 | 1. Recognize risk factors for depression, psychosis, and impulse control behaviors in patients with PD. |
| 2. Discuss the pathophysiology and treatment of depression, psychosis, and impulse control behaviors in patients with PD. |
| 3. Use CBT for the treatment of older patients. |
| 4. Discuss the empirical evidence supporting the use of CBT for treatment of older patients. |
| 5. Explain to elderly patients how psychiatric conditions can be induced by nonpsychiatric medications. |
Discussed on This Program
Amantadine HCl [Symmetrel] Chlorpheniramine maleate [Allergy, Aller-Chlor, Chlo-Amine, Chlor-Trimeton] Cimetidine [Cimetidine Oral Solution, Tagamet, Tagamet HB] Ciprofloxacin [Ciloxan, Cipro, Cipro I.V., Cipro XR] Clozapine [Clozaril] Cycloserine [Seromycin Pulvules] Diphenhydramine HCl [several trade names] Disulfiram (Antabuse) Isoniazid (isonicotinic acid hydrazide; INH) [Nydrazid] Levodopa (L-dopa) [Dopar, Larodopa] Methylprednisolone (Medrol) Metronidazole [several trade names] Nortriptyline HCl [Aventyl HCl, Aventyl HCl Pulvules, Pamelor] Ofloxacin [Floxin, Floxin Otic, Ocuflox Ophthalmic Solution] Olanzapine [Zyprexa, Zyprexa Intramuscular, Zyprexa Zydis] Paroxetine HCl [Paxil, Paxil CR] Quetiapine fumarate [Seroquel] Ranitidine HCl [Zantac, Zantac 75, Zantac EFFERdose, Zantac GELdose] Triprolidine hydrochloride [Actidil]
Suggested Reading
Cubo E et al: Cognitive and motor function in patients with Parkinson's disease with and without depression. Clin Neuropharmacol 23(6):331, 2000; Curtis LH et al: Inappropriate prescribing for elderly Americans in a large outpatient population. Arch Intern Med 164(15):1621, 2004; De Leo D et al: Pharmacological and psychotherapeutic treatment of personality disorders in the elderly. Int Psychogeriatr 11(2):191, 1999; Fick DM et al: Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med 163(22):2716, 2003; Gomez-Esteban JC et al: Use of ziprasidone in parkinsonian patients with psychosis. Clin Neuropharmacol 28(3):111, 2005; IMPACT Investigators: Improving Mood-Promoting Access to Collaborative Treatment. Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA 288(22):2836, 2002; Joffe G et al: The effect of clozapine on the course of illness in chronic schizophrenia: focus on treatment outcome in out-patients. Int Clin Psychopharmacol 11(4):265, 1996; Lynch TR et al: Dialectical behavior therapy for depressed older adults: a randomized pilot study. Am J Geriatr Psychiatry 11(1):33, 2003; Molina JA et al: Pathologic gambling in Parkinson's disease: a behavioral manifestation of pharmacologic treatment? Mov Disord 15(5):869, 2000; Oechsner M, Korchounov A: Parenteral ziprasidone: a new atypical neuroleptic for emergency treatment of psychosis in Parkinson's disease? Hum Psychopharmacol 20(3):203, 2005; Ondo WG et al: Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease. Mov Disord Mar 30[Epub ahead of print], 2005; Pinquart, M, Sörensen, S: How effective are psychotherapeutic and other psychosocial interventions with older adults? A Meta-analysis. Journal of Mental Health and Aging 7(2),207, 2001; Rosenthal MZ et al: Thought suppression and treatment outcome in late-life depression. Aging Ment Health 9(1):35, 2005; Wetherell JL et al: Psychological Interventions for Late-Life Anxiety: A Review and Early Lessons From the CALM Study. J Geriatr Psychiatry Neurol 18(2):72, 2005; Wetherell JL, Unutzer J: Adherence to treatment for geriatric depression and anxiety. CNS Spectr 8(12 Suppl 3):48, 2003; Wetherell JL et al: Anxiety symptoms and quality of life in middle-aged and older outpatients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 64(12):1476, 2003; Wilson K et al: A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry 19(8):754, 2004; Woo BK et al: The clock drawing test as a measure of executive dysfunction in elderly depressed patients. J Geriatr Psychiatry Neurol 17(4):190, 2004;
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed: Dr. Israel is a consultant for Sepracor Inc.
Dr. Hui was recorded at Parkinson’s Disease and Related Disorders: Current Knowledge and New Directions, held April 1, 2005, in Los Angeles, and sponsored by the Keck School of Medicine of the University of Southern California. Drs. Wetherell and Israel were recorded at the West Coast Geriatric Psychiatry Conference, held February 10-13, 2005, in San Diego, and sponsored by the University of California, San Diego, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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