Psychosocial Concomitants to Rehabilitation in Chronic Obstructive Pulmonary Disease

Abstract

Some chronic obstructive pulmonary disease (COPD) patients with psychiatric disease require treatment that is biologic or pharmacologic. A certain number of patients with significant psychiatric disease, (as distinguished from psychosocial or psychophysiologic problems), can be managed only with the help of psychoactive medications. At the same time, however, the guidelines for psychosocial and psychologic management apply. Once the psychiatric disease is under control, it is likely that the need of these patients for continued psychiatric/ psychological evaluation and psychotherapy will be greater than that of the patients who have not experienced a similar problem. In contrast to psychosocial and psychophysiologic problems and their accompanying emotions that afflict many or most patients with severe pulmonary disease, psychiatric disease is probably no more frequent than in patients without pulmonary disease. The distinction between psychophysiologic and psychosocial problems and significant psychiatric disease is a critical issue. The treatment of the former can often be by various psychotherapies, behavioral therapies, and social support systems, with medication as adjuncts when necessary, while treatment of the latter should initially be primarily with medications. Other types of therapy may be needed in the recovery period, but there likely will be no recovery period without the use of medications. In general, the psychiatric diseases to be concerned about are the schizophrenias, manic depressive illness (unipolar and bipolar types), and delirium (acute brain syndromes). Specific pharmacologic treatments are also available for anxiety and depression not classified in the above three categories. A review of psychiatric diseases can be obtained from any of the current textbooks of psychiatry. Patients with combined psychiatric and pulmonary disease are more likely to have serious problems than patients without such combinations. A good way to screen for possible psychiatric disease can be to identify patients with (a) marked pulmonary disease but with no complaints or no response to the reality of the disease at all; (b) those with little pulmonary disease who are incapacitated; (c) patients who overreact and feel little hope for coping with the concomitant problems. This clinical information suggests an increased probability of the patients' having a psychiatric problem but does not necessarily confirm the diagnosis. In early states of pulmonary disease, changes in psychologic activation are often associated with dyspnea only. As the disease progresses in severity, it may reach a point where increases in emotional activation of any type produce elevations in oxygen consumption and carbon dioxide production that cannot readily be compensated for physiologically because of the patient's impaired ventilation. Even minimal changes in alveolar ventilation then become difficult to accommodate. With psychologic activation, the patient with an unimpaired muscular system, (that is, one who is not paralyzed and thus can contract muscles), is likely to then develop hypoxia and possible hypercarbia. When there is a decrease in psychologic activation, there is a drop in the amount of air the patient breathes, but there is no equivalent drop in oxygen need and nutritional requirements of the skeletal muscles. Thus, any and all emotional arousal may be associated with uncomfortable symptoms because the pulmonary system then tends to deliver less oxygen than is required to meet metabolic demand. Until these symptoms are relieved, nonmedical, eg, psychosocial treatment, becomes difficult or impossible to accomplish. The secondary reaction to dyspnea, wheezing, cough, sputum production, and pain that occurs can be anxiety, fear, and/or depression that in turn serves as another emotional stimulus, further compromising the patient's physiological and emotional state. It is understandable that these people tend to avoid interpersonal contact because of the psychological stress involved. They thereby decrease psychological stressors. By using denial and repression, they lessen the impact of emotionally loaded events. The psychological defenses used to protect a failing organ system, however, are often regarded by others as socially inappropriate, since the patient may be perceived as rejecting, bland, and unresponsive. The preceding problems can be magnified many times in patients with psychiatric disorders. The role of psychoactive medications in the treatment of patients with pulmonary disease is of considerable importance, since many lack the ability to utilize other treatment techniques, and psychotherapy is often contraindicated or not effective. In addition, medications are the only practical approach to treating symptoms associated with significant psychiatric disease, in contrast to social maladjustment that may be treatable with psychotherapy. Failure to utilize these types of medications knowledgeably and with discriminating care can significantly increase morbidity and possibly mortality in the patient with pulmonary disease. In addition, psychoactive medication also can be useful as an adjunct to psychotherapy. For example, a depressed patient with severe sleep, energy, and appetite impairment may be more responsive to psychotherapeutic interventions if medication can increase energy levels and improve appetite. Otherwise, the patient may lack the energy and stamina to examine and work on his problems. The following general information should be supplemented by a review of therapeutic and nontherapeutic effects of psychoactive medications.1Freedman AM Kaplan HI Sadock BJ Comprehensive Textbook of Psychiatry II. Williams & Wilkins, Baltimore1975Google Scholar, 2Cain RM Cain NN A compendium of drugs.Drug Ther. 1975; 5: 1-16Google Scholar, 3Kalinowsky LB Hippius H Pharmacological, Convulsive, and Other Somatic Treatment in Psychiatry. Grune & Stratton, New York1969Google Scholar, 4Greenblatt DJ Shader RI Benzodiazephines in Clinical Practice. Raven Press, New York1974Google Scholar, 5Lipton MA DiMascio A Killam KF Psychopharmacology.A Generation of Progress. Raven Press, New York1978Google Scholar, 6Van Praag HM Psychotropic Drugs.A Guide for the Practitioner. Brunner/Mazel, New York1978Crossref Google Scholar, 7Forrest IS Carr JC Usdin E Phenothiazines and Structurally Related Drugs. Raven Press, New York1974Google Scholar, 8Shader RI Manual of Psychiatric Therapeutics.Practical Psychopharmacology and Psychiatry. Little Brown & Co, New York1975Google Scholar The use of psychopharmacologic agents in COPD patients must be individualized to a greater extent than is generally practiced. The reasons for this are varied but seem to be related to the age of the patient, chronicity of the disease, other concomitant diseases, and individual needs and reactions to a given drug. As a rule, the greater the age and the more chronic the disease, the lower the dose of psychopharmacologic agent advisable.8Shader RI Manual of Psychiatric Therapeutics.Practical Psychopharmacology and Psychiatry. Little Brown & Co, New York1975Google Scholar,9Eisdorfer C Farm WE Psychopharmacology and Aging. Plenum Press, New York1973Crossref Google Scholar In many patients, the dose of psychoactive medication will be one third or less than that normally prescribed to treat psychiatric disease. In addition, it is important to select agents and doses that do not depress or overly stimulate the respiratory center, do not adversely interact with pulmonary medicaments, and do not add to existing pulmonary or cardiac problems. Some hospitals now have facilities for measuring blood levels of major psychoactive medications. In such a setting, the optimal clinical response can be associated with a specific blood level, and that blood level can then be maintained. This method of determining the individualized dosage is the preferred treatment in patients with combined psychiatric disease and severe COPD. Fortunately, most psychoactive compounds have a high degree of safety in patients with pulmonary disease when used discriminately and with awareness of contraindications for given cases. Any medication is a compromise between the possible toxic side effects and the possible clinical benefits. However, even the potentially most toxic of the psychoactive agents are safe in the hands of someone who knows how and when to use them. Anxiolytic agents (Table 1) are often overused. They tend to be given in sympathy for the patients' condition and our inability to cure them rather than for specific indications. As with any medication, it is better not to prescribe anxiolytic agents if clinical indications for their administration are unclear. These are potent compounds, and prescribing them indiscriminately, (that is, to patients who may not need them or need some other type of medication such as an antidepressant or neuroleptic), can be antitherapeutic and particularly dangerous in the pulmonary disease patients. Without a clear diagnostic impression, it is likely that the only effect will be sedation, and potentiation of depression or behavioral disorganization that may further aggravate problems with pulmonary disease. The use of these agents should be limited to the attainment of short-term goals, such as overcoming an acute situational problem. Giving them over long periods of time can lead to significant problems with habituation and depression. If an anxiolytic agent has been administered in significant dosage over an appreciable period of time,withdrawal should be carried out by gradual reduction of dosage rather than abruptly. Abrupt withdrawal will result in symptoms such as nervousness, anxiety, tremors, insomnia, and in fact, most of the symptoms that occur when an alcoholic is taken off alcohol. Problems resulting from abrupt withdrawal from long-term use occur with reference to many medications, not just anxiolytics.Table 1Examples of Anxiolytic Agents (Minor Tranquilizers) *Barbiturates produce unacceptable central nervous system depression, sedation, dependency and addiction risk and have a low safety margin compared to the medications listed above, with the exception of meprobamate. For all anxiolytics listed, drowsiness or lack of attention may make operation of machinery dangerous. This is particularly so during initial treatment. Selected patients may need the usual daily dose. Respiratory depression with aggravation or onset of hypoxia and hypercarbia is always a possible complication when the anxiolytic agents are used in the COPD population.Specific MedicationIndicationsSpecial PropertiesUsual Daily Dose (Oral), mgDaily Dose in Moderate to Severe COPD (Oral), mgBENZODIAZEPINES Chlordiazepoxide (Librium)Anxiety which is impeding specific behaviors such as sleep, exercise, social interactions. Some cases of insomnia.Poor absorption by the intramuscular route. For many the drug of choice in alcohol withdrawal.10–20010–100Diazepam (Valium)Same as for chlordiazepoxidePoor absorption by the intramuscular route. Good muscular relaxant.5–505–10Clorazepate (Tranxene)Same as for chlordiazepoxide.Wide dose selection.3.75-453.75-15GLYCEROL DERIVATIVES Meprobamate (Miltown, Equanil)Not recommended. If used, same as chlordiazepoxide.May have low safety factor with overdose as compared to other anxiolytic agents.400–1600200–800DIPHENYLMETHANE DERIVATIVES Hydroxyzine (Atarax, Vistaril)Same as for chlordiazepoxide.Antihistamine Low abuse potential compared with other anxiolytic agents. Atropine-like side effects.25–20010–100* Barbiturates produce unacceptable central nervous system depression, sedation, dependency and addiction risk and have a low safety margin compared to the medications listed above, with the exception of meprobamate. For all anxiolytics listed, drowsiness or lack of attention may make operation of machinery dangerous. This is particularly so during initial treatment. Selected patients may need the usual daily dose. Respiratory depression with aggravation or onset of hypoxia and hypercarbia is always a possible complication when the anxiolytic agents are used in the COPD population. Open table in a new tab Tabled 1COMMON SIDE EFFECTS:PRECAUTIONS WITH:CONTRAINDICATIONS:DrowsinessGlaucomaHypersensitivityAtaxiaAnticoagulantsPorphyria (do not useConfusionRenal impairmentmeprobamate)Slurred speechRespiratory depressionComotose statesHeadacheHepatic impairmentSevere dependency orDizzinessPregnancyaddictionImpaired visual accomo-Withdraw slowly when useddationlong term to avoid problemsDependencysuch as convulsionsDry mouthBreast feeding mothers—medicationDifficulty handling secretionsmay be transferred via milk May occasionally produce paradoxical rage or anxiety or depression Open table in a new tab Commonly used anxiolytic agents are (a) diazepam, (b) chlordiazepoxide, (c) hydroxyzine, and (d) oxazepam. It may be interesting to note that one psychiatrist who frequently treats patients with severe pulmonary disease and is well acquainted with the effects of these agents, writes prescriptions for anxiolytic compounds only several times per year. Unlike the neuroleptics and antidepressants, these medications in low to moderate doses may cause significant respiratory depression.10Steen SN The effects of psychotropic drugs on respiration.Pharmacol Ther. 1976; 2: 717-741Google Scholar The neuroleptics (formerly called major tranquilizers) are used in the treatment of psychiatric diseases such as schizophrenia, mania, acute psychotic reactions and sometimes delirium (Table 2). In common with the antidepressants (Table 3), they are not habit-forming or addicting and are well tolerated if prescribed for the appropriate disease conditions. Neuroleptics and antidepressants are generally seen as being too powerful and dangerous, while the anxiolytic agents are considered in-ocuous. Both types of medication can have side effects in some patients, but the side effects of the neuroleptics are less difficult to counteract than those from long-term administration of anxiolytic agents in significant dosage.Table 2Examples of Neuroleptics (Major Tranquilizers)*As you move from thioridazine to haloperidol, extrapyramidal symptoms increase, and moving backward, alpha adrenergic blocking, allergic responses, sedation, atropine like effects, seizures and orthostatic hypotension generally increase. For all neuroleptics listed, drowsiness or lack of attention may make operation of machinery dangerous. This is particularly so during initial treatment. Selected patients may need the usual daily dose. Respiratory depression with aggravation or onset of hypoxia and hypercarbia is always a possible complication when the neuroleptics are used in the COPD population. Neuroleptics in general can alter sexual function and drive. Each medication in this class can produce specific types of problems. For example, thioridazine may contribute to delayed or inhibited ejaculation and chlorpromazine may contribute to a simple reduction in sexual drive. On the other hand, both may increase sexual drive and performance in specific patients. In addition, sexual dysfunction is so common in patients who need to be treated with neuroleptics that it is often difficult to know what the cause of the change in sexual function is secondary to.Specific MedicationIndicationsSpecial PropertiesUsual Daily Dose (Oral), mgDaily Dose in Moderate to Severe COPD (Oral), mgPHENOTHIAZINESThioridazine (Mellaril)Same as for chlorpromazine. When anticholinergic activity plus sedation are desired.Strongly anticholinergic compared to other neuroleptics on this chart. Inhibition of ejaculation. Pigmented retinitis in daily doses over 800 mg.50–8005–200Chlorpromazine (Thorazine)Hyperactive behavior in association with schizophrenia, mania or other definable psychiatric disease. Need to attenuate disturbing sensory stimuli. When sedation is desirable.Sedating.50–20005–200Fluphenazine (Prolixin)Same as for chlorpromazine with less sedation.Available in depot form (Prolixin Decanoate or Enanthate) which can be administered to patients who are unreliable or who prefer the convenience of not taking daily medications.2–20 (oral)Depot form 12.5 to 75 mg every 1 to 3 weeks intramuscular injection.1–10 (oral)Depot form 6.25 to 37.5 mg every 1 to 3 weeks intramuscular injection.DIHYDROLINDOLONES Molindone (Mobane)Same as for chlorpro-mazine.Apparent low cardiovascular toxicity as compared with chlorpromazine. Does not block guanethidine. Little or no experience with the drug in COPD.30–10010–30THIOTHANXENES Thiothixene (Navane)Same as for chlorpromazine.Low anticholinergic activity. May have significant antidepressant effect.5–802–20BUTYROPHENONES Haloperidol (Haldol)Same as for chlorpromazine. When sedation and cardiovascular side effects need to be avoided.The least sedating neuroleptic. The most likely to produce Parkinson type symptoms. Low cardiovascular toxicity. Low anticholinergic activity.2–401–10* As you move from thioridazine to haloperidol, extrapyramidal symptoms increase, and moving backward, alpha adrenergic blocking, allergic responses, sedation, atropine like effects, seizures and orthostatic hypotension generally increase. For all neuroleptics listed, drowsiness or lack of attention may make operation of machinery dangerous. This is particularly so during initial treatment. Selected patients may need the usual daily dose. Respiratory depression with aggravation or onset of hypoxia and hypercarbia is always a possible complication when the neuroleptics are used in the COPD population.Neuroleptics in general can alter sexual function and drive. Each medication in this class can produce specific types of problems. For example, thioridazine may contribute to delayed or inhibited ejaculation and chlorpromazine may contribute to a simple reduction in sexual drive. On the other hand, both may increase sexual drive and performance in specific patients. In addition, sexual dysfunction is so common in patients who need to be treated with neuroleptics that it is often difficult to know what the cause of the change in sexual function is secondary to. Open table in a new tab Table 3Examples of Tricyclic Antidepressants*As you go from amitriptyline to protriptyline, initial activation effect generally increases. Initial effects should be distinguished from antidepressant effect which will follow in days. Initial sedation or activation is present in hours. However, initial effect is therapeutic and demonstrates to the patient that the condition is responsive to medications. In general, avoid giving a sedating antidepressant during the day or to a patient with a retarded depression. The initial sedation may incapacitate the patient and lead to noncompliance with therapy. For all antidepressants listed, drowsiness or lack of attention may make operation of machinery dangerous. This is particularly so during initial treatment. A beneficial side effect of these medications in COPD patients may be mild bronchodilation. Selected patients may need the usual daily dose.Specific MedicationIndicationsSpecial PropertiesUsual Daily Dose (Oral), mgDaily Dose in Moderate to Severe COPD (Oral), mgAmitriptyline (Elavil)Agitated depression or prophylactic treatment of panic attacks.Strongly anticholinergic. Strongly sedating. Reportedly high incidence of cardiac complications. Administer near bedtime.50–30010–100Doxepin (Adapin or Sinequan)Same as amitriptyline plus severe insomnia.Compared with amitriptyline it is moderately anticholinergic but equally sedating. Low cardiac toxicity. Little or no effect on respiratory center. Unlikely to inhibit guanethedine in doses under 150 mg. Administer near bedtime.50–30010–100Imipramine (Presamine or Tofranil)Depression which falls between the agitated and retarded categories. Prophylactic treatment of panic attacks.Moderately anticholinergic. May be sedating. Potential cardiac complications. Administer near bedtime or during the day depending on degree of sedation.50–30010–100Despiramine (Pertofrane, Norpramin)Same as imipramineWeakly anticholinergic compared to amitriptyline. Tends to be more activating than imipramine. Lower incidence of potential cardiac complications compared to imipramine. Generally administer during the day unless sedating effect predominates.50–20010–100Protriptyline (Vivactil)Retarded depression or depression associated with loss of energy.Moderately anticholinergic. Potential cardiac complications. May be used in combination with amitriptyline or doxepin. Give the sedating antidepressant for sleep and protriptyline in the morning for energy. Administer in the morning and at noon. Activating effect should be apparent in hours.5–602.5-20* As you go from amitriptyline to protriptyline, initial activation effect generally increases. Initial effects should be distinguished from antidepressant effect which will follow in days. Initial sedation or activation is present in hours. However, initial effect is therapeutic and demonstrates to the patient that the condition is responsive to medications. In general, avoid giving a sedating antidepressant during the day or to a patient with a retarded depression. The initial sedation may incapacitate the patient and lead to noncompliance with therapy.For all antidepressants listed, drowsiness or lack of attention may make operation of machinery dangerous. This is particularly so during initial treatment.A beneficial side effect of these medications in COPD patients may be mild bronchodilation. Selected patients may need the usual daily dose. Open table in a new tab Tabled 1COMMON SIDE EFFECTS:PRECAUTIONS WITH:CONTRAINDICATIONS:Blurred visionSeizuresComatose statesDyeuriaDepressionCentral nervous systemConstipationPregnancydepressionNasal congestionRespiratory diseaseBone marrow depressionPostural hypotensionCardiac diseaseSubcortical brain damagePhotosensitivityRespiratory depressionSeriously impaired liverDrowsinessMay reverse the hypertensivefunctionFatigueaction of medications such asHypersensitivityWeight gainepinephrine, and block theUncontrolled epilepsyExtrapyramidal side effectsantihypertensive effect ofSevere retarded depressionRespiratory depressionguanethidinePotential difficultyhandling secretions Open table in a new tab Tabled 1COMMON SIDE EFFECTS:PRECAUTIONS WITH:CONTRAINDICATIONS:Dry mouthUrinary retentionAcute myocardial infarctionPotential difficulty handling secretionsCardiovascular disordersHypersensitivityBlurred visionNarrow angle glaucomaAcute schizophreniaConstipationOrganic brain syndromeManiaNauseaSchizophreniaMonoamine oxidase inhibitorsHeartburnManiaHypotensionConvulsive disordersWeight gainThyroid DiseasePregnancyPotentiation of sympathomimeticaminesBlocking guanethidine Open table in a new tab Two neuroleptics that provide reasonable examples of the benefits and problems of this class of medications are (haloperidol (a butyrophenone) and chlorpromazine (a phenothiazine). The advantage of haloperidol seemingly lies in its relatively pure, central blockade of dopamine. This dopamine blockade produces a decrease in sensory input and decreased activity of emotional centers in the brain with minimal sedation. It is the neuroleptic of choice if the patient has hypotension or potentially serious cardiac problems because it has low cardiac toxicity and may have no effect on blood pressure. A problem with haloperidol when given by the oral and intramuscular route is the development of extrapyramidal signs and symptoms. These side effects can be particularly distressing to patients with restrictions in the ability to move air. Several recent studies have shown that the intravenous use of haloperidol is safe and effective in medical and surgical patients and that there is very little or no production of extrapyramidal problems. From initial data, it would appear that during psychiatric emergencies in medical and surgical patients, this medication may be safer when given by the intravenous route! It should be noted that butyrophenones have been found to produce occasional bronchoconstriction.10Steen SN The effects of psychotropic drugs on respiration.Pharmacol Ther. 1976; 2: 717-741Google Scholar Chlorpromazine is useful in situations in which a reduction in both blood pressure and sensory input, coupled with sedation, is clinically desirable. Less well known complications of chlorpromazine treatment include hyperthermia and the formation of antinuclear antibodies.11Quismorio FP Fjarnason DF Kiely WF et al.Antinuclear antibodies in chronic psychotic patients treated with chlorpromazine.Am J Psychiatr. 1975; 132: 1204-1206Crossref PubMed Scopus (31) Google Scholar Chlorpromazine has been implicated in the uncoupling of oxidative phosphorylation, thus blocking the formation of adenosine triphosphate (ATP).12Gatz EE The mechanism of induction of malignant hyperpyrexia based on in vitro to in vivo correlative studies.in: Gordon RA International Symposium on Malignant Hyperthermia. Thomas, Springfield, 1111972Google Scholar This can lead to the production of useless heat and subsequent hyperthermia. A more common reaction to chlorpromazine, however, is hypothermia related to decreased muscle tone and peripheral alpha-adrenergic blockade. This blockade is also associated with the production of hypotension. The hypotension may be aggravated by the concomitant use of sympathomimetic medications, such as epinephrine, that have both alpha- and beta-adrenergic action. To support blood pressure in the unusual circumstance that it may be necessary, the addition of a strong alpha stimulant (such as dopamine or norepinephrine) is recommended. Rapid treatment of extrapyramidal reactions (more common with haloperidol than with chlorpromazine) is important in maintaining unimpaired respiratory movements. These reactions initially should be treated with intravenous administration of benztropine mesylate, 1 mg, or diphenhydramine hydrochloride, 50 mg. Oral maintenance therapy can be accomplished with any of the antiparkinson medications, such as benztropine mesylate or pro-cyclidine hydrochloride. In doses above 400 mg daily, up to 50 percent of patients treated with chlorpromazine may develop antinuclear antibodies, and a rare patient will develop a lupus erythematosis-type syndrome. The lupus syndrome appears to be identical to the reaction to hydralazine hydrochloride and procainamide hydrochloride and is not permanent if the medication is withdrawn. It should be noted that the antidepressants are also implicated in the production of hyperthermia. This appears to be related to central hypothalmic and anticholinergic action. As a general rule, the more neuroleptics, antidepressants and antiparkinson medications prescribed for any given patient, the higher the probability of clinically significant hyperthermia. In the treatment of depression, it is helpful to have information on the clinical use of antidepressants for the following three purposes: sedating, illustrated by doxepin; activating, illustrated by protriptyline; and intermediate, illustrated by imipramine. In general, these compounds potentiate the action of steroids and also are compatible with or potentiate bronchodilators. Doxepin is the antidepressant of choice in agitated, depressed patients with COPD. In addition to its antidepressant characteristics, it is sufficiently sedating to reduce or eliminate the agitation. The sedative effect is apparent in minutes or hours, while the antidepressant effect may not appear for several weeks. As with other antidepressants, it appears to have little or no effect on the respiratory center, and it seems to act as a mild bronchodilator.10Steen SN The effects of psychotropic drugs on respiration.Pharmacol Ther. 1976; 2: 717-741Google Scholar,13Knapp PH Mathe AA Vachon L Psychosomatic aspects of bronchial asthma.in: Reiss EB Segal M Bronchial Asthma—Mechanisms and Therapeutics. Little Brown & Co, New York1976Google Scholar Protriptyline is the antidepressant of choice in retarded, depressed patients with low drive and motivation. An activating effect may appear in hours, but as with doxepin, the antidepressant effect may not appear for days or weeks. Imipramine falls in between doxepin and protriptyline and should be used when clear sedation or activation is not needed. As a general rule, patients will not adapt well to doxepin if it is given during the day, or to protriptyline if it is given at night. To obtain optimal therapeutic effect, advantage should be taken of the initial sedative and activating characteristics by prescribing them at times when sedation or activation will not interfere with the patient's life. It should be noted that the neuroleptics have a similar biphasic effect. The immediate effect may be calming, sedating, or both, but the antipsychotic effect may take days or weeks to become apparent. A review of the cardiovascular effects of the anti-depressants is essential.14Burrows GD Vohra J Hunt D et al.Cardiac effects of different tricyclic antidepressant drugs.Br J Psychiatr. 1976; 129: 335-340Crossref PubMed Scopus (88) Google Scholar In general, doxepin is the least cardiotoxic. However, after considering the anticholinergic and sympathomimetic action of these medications, one is left with the fact that they have a quinidine-like action that may well be beneficial for patients with premature ventricular auricular contractions. In utilizing the antidepressants and neuroleptics, it is important to remember that blood levels may have little relationship to oral dose, and cellular levels may be poorly related to either. Since these compounds may have a therapeutic window, above or below which there will be no positive clinical effects, it is essential to maintain optimal blood levels of major psychoactive medications. This is particularly so for the tricyclic antidepressants. In such a setting, the desired clinical response can be associated with a specific blood level, then maintained. This method of determining dosage is the preferred one in patients with combined psychiatric disease and pulmonary disease. In addition to the increased effectiveness of the treatment, it is unusual to have significant cardiac problems when these medications are given within a reasonable therapeutic window. Understanding lithium therapy has become increasingly important as clinical studies continue to demonstrate its effectiveness in controlling recurrent mania, depression, or cyclic swings from mania to depression. Mania may be treated initially with a neuroleptic, and depression with an antidepressant. However, lithium should be started concomitantly. The starting dose of lithium is generally from 300 to 900 mg per day. This dose may require modification if the patient is taking theophylline or a diuretic, since theophylline tends to cause an increased excretion of lithium, and most diuretics will decrease excretion of lithium. In addition, lithium excretion may vary with salt intake which should thereby be kept stable during lithium administration. A fasting morning level of lithium (nine to ten hours after the evening dose) of 0.5 to 1.0 mEq/L is usually therapeutic in patients with moderate to severe lung disease. It may take three to ten days to equilibrate at a therapeutic blood level. Lithium usually has a seven to ten day lag between the onset of therapy and the therapeutic response. When the maintenance dose is reached, the neuroleptic or antidepressant can usually be withdrawn. Note that some COPD patients obtain good therapeutic effects from blood levels of 0.2 mEq/L. Recent data indicate that lithium may produce significant renal problems.15Ayd FJ Lithium-induced nephrotoxicity: a further report.Int Drug Ther Newsletter. 1978; 13: 25-28Google Scholar This information should be reviewed by physicians contemplating its use in COPD patients. Patients should be monitored carefully for signs of toxi