Effect of desipramine on control of ventilation and depression scores in patients with severe chronic obstructive pulmonary disease

doi:10.1016/0165-1781(85)90036-8

Psychiatry Research

Volume 15, Issue 1, May 1985, Pages 25-32

https://doi.org/10.1016/0165-1781(85)90036-8 Get rights and content

Abstract

Decreased ventilatory responses to carbon dioxide (CO₂) correlate with elevated scores on tests for depression in normal subjects and with episodes of endogenous depression in psychiatric patients. Patients with severe chronic obstructive pulmonary disease (COPD) frequently develop resting hypercapnia due to impaired ventilatory mechanics or drive, and may also have elevated scores on tests for depression. Tricyclic antidepressant drugs can improve ventilatory mechanics and possibly drive. We hypothesized that antidepressant drugs might enhance ventilatory drive and improve arterial blood gases in patients with severe COPD and that these improvements might correlate with improvement in depression scores. Therefore, we studied the effects of desipramine versus placebo on spirometry, resting arterial blood gases, hypercapnic ventilatory and mouth occlusion pressure responses, and scores on the Beck and Zung self-rated depression scales. In our patients the resting arterial CO₂ (P_aCO₂) was found to depend almost equally on ventilatory mechanics and drive. In addition, patients with higher depression scores tended to have a lower P_aCO₂ when the severity of airways obstruction was taken into consideration. In a 16-week, double-blind, crossover comparison of desipramine with placebo, both treatments led to significant improvement in depression scores. Desipramine had no effects on resting P_aCO₂, spirometry, or ventilatory control.

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A placebo control study conducted by Gordon and colleagues indicated no difference between COPD patients treated incrementally with 25–100 mg of despiramine to the placebo control over an eight week period (Gordon et al., 1985; Yohannes and Alexopoulos, 2014b). Of the original 13, two patients withdrew from the study due to adverse side-effects while five others withdrew due to other problems (Gordon et al., 1985; Yohannes and Alexopoulos, 2014b). Doxepin was tested in a six week randomized placebo control study composed of 12 COPD patients (Light et al., 1986; Yohannes and Alexopoulos, 2014b).
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Antidepressants have been inadequately investigated in depressed COPD patients. Placebo-controlled studies showed that doxepin, desipramine, and paroxetine were no better than placebo in improving COPD patients' moods.3,30,31 Meanwhile, a 12-week placebo-controlled study of depressed or dysthymic COPD patients concluded that nortriptyline is more efficacious than placebo in reducing depressive symptoms, anxiety, respiratory symptoms, overall physical comfort, and day to day functioning.32
Depression worsens most treatment outcomes in medically ill older adults. Chronic medical illnesses weaken and demoralize patients and compromise their ability to adhere to treatments requiring consistency and effort. Acute medical illnesses create a psychosocial storm that finds patients and their ecosystem unprepared. We describe two intervention models that can be used to target and personalize treatment in depressed, chronically, or acutely medically ill older adults. The Personalized Adherence Intervention for Depression and COPD (PID-C) is a model intervention for depressed patients with chronic medical illnesses. It targets patient-specific barriers to treatment engagement and aims to shift the balance in favor of treatment participation. PID-C led to higher remission rates of depression, reduction in depressive symptoms, and reduction in dyspnea-related disability. The addition of problem-solving training enables patients to use resources available to them and hopefully improve their outcomes. Ecosystem-focused therapy (EFT) is a model intervention for depression developing in the context of an acute medical event. It was developed for patients with poststroke depression (PSD) and targets five areas, part of the “psychosocial storm” originating from the patient's sudden disability and the resulting change in the patient's needs and family's life. A preliminary study suggests that EFT is feasible and efficacious in reducing depressive symptoms and signs and disability in PSD.
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The effect size for the difference in reduction of depressive symptoms between placebo and nortriptyline was d = −1.07. A second study suggested at least some improvements in depressive symptoms after eight weeks of desipramine, but similar effects were found after eight weeks of placebo treatment.38 In a double-blind crossover trial regarding hospitalized veterans, doxepin hydrochloride did not lead to significant improvements in exercise capacity or depression scores.39
Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease characterized by progressive and only partially reversible symptoms and by considerable negative consequences such as reductions in functional status and quality of life. Comorbid depression is highly prevalent in patients with COPD and related to a worse course of the disease. Despite its negative impact, depression often remains unrecognized and untreated in COPD patients. This review summarizes the current state of findings from studies examining the effects of antidepressant treatments in patients with COPD. Reviewed treatment options are antidepressant medical therapy and cognitive-behavioral therapy (CBT). Antidepressant medical trials include treatments with selective serotonin reuptake inhibitors (SSRI) or tricyclic antidepressants (TCA); CBT was applied using various components. Across both treatment types, the majority of studies included patients with a wide range of psychiatric conditions and especially comorbid symptoms of anxiety were often not controlled. Furthermore, greatly varying instruments and methods for assessing depressive symptoms, small sample sizes and rather heterogeneous results were observed. This makes the comparison of treatment options rather difficult and prevents definite conclusions. However, some important implications valuable for further research were obtained. Some limited data suggested that SSRI might show fewer side effects than TCA. A few antidepressants as well as beneficial effects in other outcomes were observed after antidepressant medical treatment. More clearly, CBT showed some potential in terms of improvements in depressive symptoms, and also in other outcome measures. Patient compliance seems more promising for CBT than for antidepressant medical treatment. Overall, the reviewed studies suggest some promising effects for both treatment types and effect sizes in studies with significant antidepressant effects were reasonable. However, future randomized controlled trials comparing antidepressant medical and cognitive-behavioral therapy will be essential to assess distinct and most favorable treatment effects. Because recent data is often limited, sound diagnostic criteria of depression and adequate sample sizes are necessary to draw firm conclusions on the effects of these antidepressant treatment options in patients with COPD and comorbid depression.
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Citation Excerpt :
Our results differ in important respects from previous studies. Previous studies mostly controlled for a limited number of confounding factors such as on age and sex,7,23–26 or education and social class.23,27 Also most COPD patients have multiple co-morbid medical illnesses and use multiple medications, and these are not taken into account in previous studies.
Depression occurs commonly among patients with COPD, but the independent association of depression and COPD and the effect of depression on COPD outcomes are not well established.
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Effect of desipramine on control of ventilation and depression scores in patients with severe chronic obstructive pulmonary disease

Abstract

Journal of Psychosomatic Research

Chest

Chest

Clinics in Chest Medicine

Chest

Psychosomatics

Clinics in Chest Medicine

Chest

Pharmacology and Therapeutics

Respiration Physiology

DSM-III: Diagnostic and Statistical Manual of Mental Disorders

Effects of hypercapnia and inspiratory flow-resistive loading on respiratory activity in chronic airways obstruction

Journal of Clinical Investigation

Aminophylline improves diaphragmatic contractility

New England Journal of Medicine

The effects of amitriptyline on pulmonary ventilation and the mechanics of breathing

Psychopharmacologia

Depression: Causes and Treatment

Effect of personality on alveolar ventilation in patients with chronic airways obstruction

British Medical Journal

Respiratory ventilation and carbon dioxide levels in syndromes of depression

British Journal of Psychiatry

Central regulation of respiration by endogenous neurotransmitters and neuromodulators

Annual Review of Physiology