THE MIND-BODY CONNECTION
| DEPRESSION IN THE CHRONICALLY ILL —Roger J. Cadieux, MD, Clinical Professor of Psychiatry, Pennsylvania State University College of Medicine, Hershey |
| Cases: man who claimed he had chronic anxiety—had classic symptoms of anxiety, but also had elevated thyroid-stimulating hormone (TSH) due to hyperthyroidism; woman who said she was profoundly fatigued and depressed—met all criteria for major depressive disorder (MDD), but also had Hb 8 g/dL, indicative of anemia; woman self-referred for depression—had all vegetative signs of MDD, but also pervasive unreasonable guilt feelings (suggestive of psychotic features), and complaints of abdominal fullness, pain, and chronic cramps; had pancreatic cancer (anxiety and depression first symptoms of pancreatic cancer) |
| Depression in elderly population: underestimated and frequently undiagnosed; in many patients, depression, anxiety, and psychosis associated with serious medical illness |
| Major depression: lifetime prevalence 5% to 17% in United States; prevalence twice as high among women (women live longer than men, but have higher levels of morbidity); depression characterized by significant morbidity and high mortality from suicide; because of pervasive hopelessness of untreated depression, patients often see suicide as only way to deal with emotional pain; elderly people seldom admit they are depressed, but readily admit to having vegetative symptoms; depression chronic, recurrent, but highly treatable disorder |
| Disability and cost issues: depression leading cause of disability; Alzheimer’s disease most costly illness, followed by heart disease and depression; economic cost of depression $43 billion annually; most costs indirect; direct costs $12.4 billion; suicide cost $7.5 billion; medication accounts for only 2% of total cost; work—speaker feels depressed patients should continue working unless suicidal and needing hospitalization |
| Obstacle in primary care: most depressed people seeing primary care physician (PCP) typically complain of physical symptoms only; those seeing psychiatrists often acknowledge presence of anxiety, depression, or thought disorder; point—suspect depression if someone presents with multiple physical complaints involving several body systems |
 | Speaker’s approach to patients referred for suspected depression: reassure them they are physically ill, but also state they have “an issue” making illness worse; advise that medication “generally classified as an antidepressant” may help relieve symptoms, then begin therapeutic trial with that drug |
| Major medical disorders and depression: cerebrovascular accidents (CVAs)—depression almost universal among stroke patients; speaker recommends prophylactic antidepressants; chronic pain—patients need interventions for comorbid depression and anxiety; Parkinson’s disease—associated with depression and dementia; 30% to 40% of patients eventually develop all vegetative symptoms of MDD; another 30% present with cognitive impairment; therefore, treat cognitive impairment and depression, as well as movement disorder; dysthymia—requires lifetime treatment with antidepressants (response rate 30%-40% vs 75%-80% for MDD); postpartum depression—more severe than postpartum blues (occur closer to delivery than postpartum depression); diabetes—some metabolic changes affect central nervous system (CNS); ≈30% of diabetics also depressed; HIV—biochemical abnormalities and immune system failure can trigger cascade of events leading to major depression; coronary artery disease—associated with high rate of depression |
| Points: outpatients with major medical problems less likely to be diagnosed with MDD than hospitalized patients; undertreatment major problem in caring for depressed patients (goal to treat to remission, then keep them there) |
| Pain and depression: prevalence of depression 20% in those with limb pain, 20% to 30% with migraine, 30% to 45% with chronic low back pain, 30% to 60% with facial pain, and 60% with fibromyalgia; depression rate also high for those with irritable bowel syndrome (IBS); red flags for depression—failure of analgesics to relieve chronic pain; multiple sites of pain; psychologic factors, eg, low self-esteem (≤5 on scale of 1 to 10); suicide—>50% of chronic pain patients have at least thought about suicide |
| Approach to chronic pain patients: ask about food intake, quality of sleep, relationships and intimacy; also ask whether they find themselves crying and not knowing why |
| Myocardial infarction (MI) and depression: 1 study found the chances for MI mortality 4 times greater in those with preexisting depression; consider comorbid depression in MI patients |
| Metabolic syndrome (syndrome X): characterized by hypertension, visceral obesity, dysregulation of plasma lipids, and, possibly, diabetes; patients with stress, depression, tension, and anger 1.5 times more likely to develop this syndrome |
| Diabetes: associated with at least 2-fold increased risk of developing MDD; depressed diabetic at increased risk for diabetic retinopathy and more likely to become insulin resistant |
| Depression and anxiety: associated with cognitive changes (problems with perception, thought, and memory); high rate of depresson in patients with metastatic cancer; viral infections present almost universally with anxiety, whereas bacterial infections present with fatigue and “body shutdown”; endocrinopathies almost always associated with affectual disorder |
| Drugs that can exacerbate or trigger depressive episodes: corticosteroids (eg, prednisone 5-10 mg/day) can cause depression, hypomania, euphoria, and manic episodes; methylphenidate (Ritalin); dextroamphetamine; minor tranquilizers; cimetidine (Tagamet) can cause delirium, depression, and impotence; cardiovascular agents, particularly older nonspecific agents |
| Manifestations suggestive of depression: prolonged illness; total body fatigue; insomnia; psychomotor retardation; weight changes (usually weight loss); difficulties with thought process and concentration; feelings of hopelessness, helplessness, and sadness |
| Patients with overlapping symptoms of anxiety and depression: difficult to treat, as not all antidepressants of equal efficacy in treating anxiety; some antidepressants exacerbate anxiety |
| Issues complicating drug treatment of depression: response (50% of treated patients get better); remission (patient feels relieved); relapse; misdiagnosis or underdiagnosis; medication side effects; comorbidities; patient compliance |
| Antidepressants: older tricyclics—include imipramine (Tofranil), amitriptyline (Elavil), and doxepin (Sinequan); seldom used today as primary agents for depression, but sometimes used as augmentation agents for treating pain; effective in treating depression, but have anticholinergic and sedative side effects; amoxapine (Asendin)—no longer used for depression; antipsychotic agent; can cause tardive dyskinesia; bupropion (Wellbutrin)—mainly affects norepinephrine; avoid use in anxious depressed patients; sometimes used as augmentation agent; trazodone (Desyrel)—main use today to induce sleep (diphenhydramine [Benadryl] no longer advised for sleep because of anticholinergic effects); may induce delirium in frail elderly patients |
| Selective serotonin reuptake inhibitors (SSRIs): current drugs of choice; agents include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro); those that treat anxiety and depression include Zoloft, Paxil, Celexa, and Lexapro, but not fluoxetine; points—Prozac has longest half-life (≈300 hr); watch for development of sexual side effects (eg, impotence, loss of libido) in ≈2 wk in patients on Prozac; Prozac, Zoloft, and Paxil associated with high protein binding (therefore, watch for bleeding in patients on warfarin [Coumadin]); Paxil has highest potential for inhibition of cytochrome P450 and, therefore, for drug interactions, followed by Prozac, Zoloft, and Celexa (Lexapro and venlafaxine [Effexor] probably have “zero effect” on cytochrome P450 system); Paxil has highest anticholinergic effect (avoid in frail medically ill patients) |
| Venlafaxine: newer agent with dual action for treating depression; norepinephrine effects predominate when dose exceeds 75 mg; tends to increase pulse and blood pressure, so avoid use in anxious patients, poststroke patients, and those with hypertension |
| Duloxetine (Cymbalta): another dual-action agent; marketed for medically ill depressed patients; has short half-life; protein binding ≈90%; interferes to some degree with cytochrome P450 system; discontinuation rate 10% to 14%; avoid in patients with hepatic insufficiency |
| Response rates to antidepressant drugs: ≈60% get full response, 20% get partial response, and 20% get no response; comments—for those with partial responses, first maximize antidepressant dosage, then consider adding augmentive agent eg, lithium (low dose, ie, serum level 0.2-0.4 mEq/L), buspirone, possibly mirtazapine; avoid adding levothyroxine (T4 ), triiodothyronine (T3 ), desipramine, amitriptyline; may add mini-dose of atypical antipsychotic agent if psychotic equivalents present |
| New National Institute of Mental Health (NIMH) guidelines for treating depression: treat first episode at least 6 mo; treat second episode at least 9 to 12 mo; lifetime treatment indicated for patients with third episode, those who are suicidal, and those >60 yr of age who have one episode |
| SCHIZOPHRENIA, ATYPICAL ANTIPSYCHOTICS, AND PHYSICAL PROBLEMS —J. Jewel Shim, MD, Clinical Instructor in Psychiatry, University of California, San Francisco, School of Medicine, and Staff Physician, Langley Porter Psychiatric Institute, San Francisco |
| Schizophrenia: hallmark impairment in reality testing; often results in global effects, ie, impairment in many or all areas of functioning (eg, self care, health behaviors, medical follow-up, interpersonal relationships, occupational functioning) |
| Types of symptoms: positive—hallucinations (primarily auditory); delusions (fixed false beliefs); disorganized speech and behavior; negative symptoms—flattening of affect; alogia (impoverished speech); avolition (lack of motivation); anhedonia |
| Manifestations of schizophrenia: “narrowing down of individual’s world”; decreased sense of purpose and pleasure; diminished social interaction; reduced attention to self care and health behaviors; reduced life expectancy by ≈20% (57 yr for men, ≈65 yr for women) |
| Typical antipsychotics: low-potency agents—have anticholinergic, antihistaminic, and α-adrenergic side effects; tardive dyskinesia can develop with long-term use; associated with lower incidence of extrapyramidal symptoms (EPS) than high-potency agents; chlorpromazine (Thorazine) in this category; high-potency agents—associated with high degree of EPS (eg, parkinsonism, dystonia, akathisia), tardive dyskinesia, elevated prolactin levels (resulting in amenorrhea, galactorrhea, sexual dysfunction, and osteoporosis); cause less sedation and weight gain than low-potency agents |
| Atypical antipsychotics: have both serotonin and dopamine antagonist properties; effective in treating positive and negative symptoms of schizophrenia (typical agents better at treating positive symptoms than negative symptoms); associated with lower incidence of EPS; current first-line agents for treating schizophrenia |
| Specific agents: clozapine (first agent released); risperidone; olanzapine; quetiapine; ziprasidone; aripiprazole (newest agent); comments—these agents linked to variety of medical problems, including weight gain, diabetes, hyperlipidemia, hypertension, cardiovascular disease, osteoporosis, and metabolic syndrome (prevalence ≈25% among all Americans and 37% to 50% among those with schizophrenia) |
| Obesity: prevalence among schizophrenics 40% to 60%; lower socioeconomic status limits access to healthcare and to lower-calorie foods with high nutritional value; clozapine most likely to cause weight gain, followed by olanzapine and quetiapine; risperidone intermediate, and weight gain least likely with aripiprazole; remarks—weight gain associated with high affinity for histamine-1 receptor (direct effects on eating; sedation and resultant inactivity) and with serotonin (5HT2C ) receptor; weight gain most rapid during first 12 wk of therapy; studies suggest weight gain may continue ≤4 yr on clozapine; use of other psychotropic agents (eg, lithium, valproate) may compound weight gain; patients on clozapine need to consume only 500 additional calories daily to gain weight; nonwhites particularly vulnerable to weight gain; weight gain can lead to noncompliance and requests to discontinue drug |
| Intervention: imperative in patients who gain >5% of initial weight within first 10 wk of treatment (high risk for metabolic syndrome); consider switching to agent less likely to increase weight; minimize use of other psychotropic drugs associated with weight gain; provide education and encourage lifestyle changes; refer patient to specialist in weight loss and/or to programs, eg, Weight Watchers; consider pharmacologic interventions |
| Drugs for reducing weight: have limited success among schizophrenics; avoid sympathomimetic amines (can exacerbate psychosis); sibutramine, orlistat, amantadine, H2 -blockers (eg, start nizatidine with antipsychotic) and topiramate; several have CNS interactions, so use with caution; orlistat probably preferred agent |
| Type 2 diabetes: prevalence 2 to 4 times higher among schizophrenics; all classes of antipsychotics linked to new-onset diabetes; remarks—type 2 diabetes and problems of glucose metabolism can occur in absence of weight gain; most new cases occur during first 6 mo of therapy, often within days of starting atypical agent; clozapine and olanzapine most frequently associated with abnormal glucose metabolism; prevalence of type 2 diabetes higher among those on atypical agents than those on typical agents; interventions—try lowering dosage or stopping drug; consider switching to another agent; encourage diet and other lifestyle changes; improve compliance by encouraging regular medical check-ups |
| Dyslipidemia: typical as well as atypical agents associated with elevated lipids; studies suggest lipid profiles can improve if patients on clozapine or olanzapine switch to risperidone or ziprasidone; interventions—strive for weight reduction; adjust diet; try lipid-lowering agents; switch to agent less likely to cause hyperlipidemia |
Educational Objectives
| The goal of this program is to educate the listener about the link between chronic diseases and psychiatric disorders. After hearing and assimilating this program, the clinician will be better able to: |
| 1. Identify depression in patients with multiple physical complaints. |
| 2. Screen for depression in patients with various chronic illnesses (eg, stroke, cancer, chronic pain, Parkinson’s disease, HIV, coronary artery disease, diabetes, endocrinopathies). |
| 3. Prescribe antidepressant medications to patients who also have underlying medical disorders. |
| 4. Recognize the physical disorders associated with schizophrenia and the typical and atypical antipsychotic agents used for treating it. |
| 5. Minimize problems associated with the use of atypical antipsychotic agents (eg, obesity, type 2 diabetes, dyslipidemia). |
Discussed on This Program
Amantadine HCl [Symmetrel] Amitriptyline HCl [Elavil] Amoxapine [Asendin] Aripiprazole [Abilify] Bupropion HCl [Wellbutrin, Wellbutrin SR, Zyban] Chlorpromazine HCl [Thorazine, Thorazine Spansules] Cimetidine [Cimetidine Oral Solution, Tagamet, Tagamet HB] Citalopram HBr [Celexa] Clozapine [Clozaril] Desipramine HCl [Norpramin] Dextroamphetamine sulfate [Dexedrine, Dexedrine Spansules, DextroStat] Diphenhydramine HCl [Benadryl, others] Doxepin HCl [Adapin, Sinequan, Sinequan Concentrate, Zonalon] Duloxetine [Cymbalta] Escitalopram oxalate [Lexapro] Fluoxetine HCl [Prozac, others] Imipramine HCl [Tofranil] Levothyroxine sodium (T4 ; L -thyroxine) [Levothroid, Levoxyl, Synthroid, Unithroid] Liothyronine sodium (triiodothyronine, T3 ) [Cytomel, Triostat] Lithium [Eskalith, Eskalith CR, Lithobid, Lithonate, Lithotabs] Mirtazapine [Remeron, Remeron SolTab] Methylphenidate HCl [Ritalin, others] Olanzapine [Zyprexa, Zyprexa Intramuscular, Zyprexa Zydis] Orlistat [Xenical] Paroxetine HCl [Paxil, Paxil CR] Prednisone (several trade names) Quetiapine fumarate [Seroquel] Risperidone [Risperdal, Risperdal Consta, Risperdal M-TAB] Sertraline HCl [Zoloft] Sibutramine HCl [Meridia] Topiramate [Topamax] Trazodone HCl [Desyrel, Desyrel Dividose] Valproate sodium [Depacon] Venlafaxine HCl [Effexor, Effexor XR] Warfarin sodium [Coumadin] Ziprasidone HCl [Geodon]
Suggested Reading
Alexopoulos GS: Depression in the elderly. Lancet 365:1961, 2005; Baptista T et al: Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management, and research perspectives. Pharmacopsychiatry 35:202, 2002; Bergman RN, Ader M: Atypical antipsychotics and glucose homeostasis. J Clin Psychiatry 66:504, 2005; Bhogal SK et al: Heterocyclics and selective serotonin reuptake inhibitors in the treatment and prevention of poststroke depression. J Am Geriatr Soc 53:1051, 2005; Blashki G et al: Managing schizophrenia in general practice. Aus Fam Physician 33:221, 2004; Chue P: The assessment and management of antipsychotic-associated metabolic disturbances from a psychiatric perspective. Can J Psychiatry 49:200, 2004; Epperson CN: Postpartum major depression: detection and treatment. Am Fam Physician 59:2249, 1999; Hackett ML et al: Management of depression after stroke: a systemic review of pharmacological therapies. Stroke 36:1098, 2005; Holt RIG et al: Schizophrenia, the metabolic syndrome, and diabetes. Diabetes Med 21:515, 2004; Keith SJ, Kane JM: Partial compliance and patient consequences in schizophrenia: our patients can do better. J Clin Psychiatry 64:1308, 2003; Kennedy GJ, Marcus P: Use of antidepressants in older patients with comorbid medical conditions: guidance from studies of depression in somatic illness. Drugs Aging 22:273, 2005; Leucht S et al: Lithium for schizophrenia revisited: a systemic review and metaanalysis of randomized controlled trials. J Clin Psychiatry 65:177, 2004; Lim SL, Kim JH: Cognitive processing of emotional information in depression, panic, and somatoform disorder. J Abnorm Psychol 114:50,2005; Lustman PJ, Clouse RE: Depression in diabetic patients: the relationship between mood and glycemic control. J Diabetes Complications 19:133, 2005; Rowan PJ et al: Depressive symptoms have an independent, gradient risk of coronary heart disease incidence in a random, population-based sample. Ann Epidemiol 15:316, 2005; Sharpe JK, Hills AP: Atypical antipsychotic weight gain: a major clinical challenge. Aus N Z J Psychiatry 37:705, 2003; Simon GE et al: Clinical and functional outcomes of depression treatment in patients with and without chronic medical illness. Psychol Med 35:271, 2005; Sprague DA et al: Selection of atypical antipsychotics for the management of schizophrenia. Ann Pharmacother 38:313, 2004; Whitehead C et al: Antidepressants for the treatment of depression in people with schizophrenia: a systematic review. Psychol Med 33:589, 2003; Wirshing DA: Schizophrenia and obesity: the impact of antipsychotic mediations. J Clin Psychiatry 65(Suppl 18):13, 2004.
Faculty Disclosure
In adherence with 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. For this issue, the faculty reported nothing to disclose.
Dr. Cadieux was recorded March 14, 2005, at the 29th Semi-Annual Family Practice Review, sponsored by the Temple University School of Medicine and Lancaster General Hospital, held in Lancaster, Pennsylvania. Dr. Shim spoke March 11, 2005, at Psychiatry for Primary Care, sponsored by the University of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for making this issue possible.
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