COPD: How to manage comorbid depression and anxiety
Psychiatrists can help oxygen-starved patients breathe more easily and get full benefit from medical treatments.
Mirtazapine, which has been shown to stimulate appetite, can be considered for patients with prominent anorexia or if dyspnea frequently interferes with eating.
Tricyclic antidepressants and monoamine oxidase inhibitors are rarely considered first-line for COPD patients but may help in some clinical instances, such as in younger or middle-aged patients with chronic pain. Dosages for chronic pain generally are much lower than therapeutic dosages for depression. For example, amitriptyline is usually given at 25 mg/d for chronic pain and at 50 to 100 mg/dfor depression.
Table 1
Interactions between selected psychotropics and drugs used by COPD patients
| Psychotropic | Potential interactions |
|---|---|
| Alprazolam | Itraconazole, fluconazole, cimetidine increase alprazolam levels |
| Bupropion | Lowers seizure threshold, so use with other drugs with seizure-causing potential (eg, theophylline) requires caution May increase adverse effects of levodopa, amantadine |
| Buspirone | Erythromycin, itraconazole increase buspirone levels |
| Diazepam, lorazepam | Theophylline may decrease serum levels of these drugs |
| Divalproex | May increase prothrombin time and INR* in patients taking warfarin |
| Fluoxetine | May increase prothrombin time and INR in patients taking warfarin |
| Nefazodone | Could increase atorvastatin, simvastatin levels |
| Paroxetine | May interact with warfarin Cimetidine increases paroxetine levels Reports of increased theophylline levels |
| Risperidone | Metabolized by CYP-450 2D6 enzyme; potential exists for interactions, but none reported |
| INR: International normalized ratio, a standardized measurement of warfarin therapy effectiveness. | |
Tricyclics, however, may cause excessive sedation, orthostatic hypotension, confusion, constipation, and urinary retention. These effects can be debilitating in older patients.
Nefazodone is a potent inhibitor of the CYP-450 3A4 isoenzyme and may increase levels of triazolam and alprazolam. Levels of the lipid-lowering agents atorvastatin and simvastatin may increase threefold to fourfold when nefazodone is added. Use nefazodone with caution in patients taking digoxin, because nefazodone is 99% bound to serum proteins and may increase serum digoxin to a dangerous level. Nefazodone also carries a risk of hepatic failure, so hepatic enzyme levels should be monitored.9
Figure Destruction of air spaces and capillaries in emphysema
Many COPD patients have a mixture of emphysema and chronic bronchitis. Emphysema is characterized by damaged alveoli, loss of elasticity of airways (bronchioles and alveoli), alveoli compression and collapse, tearing of alveoli walls, and bullae formation. In chronic bronchitis, the bronchial walls are inflamed and thickened, with a narrowing and plugging of the bronchial airways.Table 1 lists selected psychotropics and their potential interactions with drugs commonly taken by COPD patients.
CASE REPORT: COPD AND ANXIETY
Ms. P, age 60, is hospitalized for an exacerbation of COPD, which was diagnosed 10 years ago. She is intubated and ventilated after developing pneumonia-related respiratory failure. After a 2-week hospitalization, her pulmonologist tries to wean her off the ventilator, but episodes of panic and dyspnea result in significant oxygen desaturations.
The patient is transferred to a rehabilitation facility. A psychiatrist is consulted and discovers a 10-year history of anxiety that had been managed with lorazepam, 1 mg tid, and sertraline, 50 mg/d.
On evaluation, Ms. P is sweating, tremulous, and hyperventilating. She cannot speak, mouth words, or nod because of her respiratory distress. During her hospitalization she has been receiving albuterol and ipratropium nebulized every 4 hours; intravenous methylprednisolone, weaned from 40 mg to 10 mg every 6 hours; sertraline, 50 mg/d; clonazepam, 1 mg qid; theophylline, 400 mg/d, and several intravenous antibiotics. Ciprofloxacin, 500 mg bid, was recently added for a urinary tract infection.
Table 2
Drugs commonly used to treat COPD and their potential psychiatric side effects
| Drug | Action | Possible psychiatric side effect |
|---|---|---|
| Albuterol | Short-acting bronchodilator | Anxiety |
| Salmeterol | Long-acting bronchodilator | Anxiety, especially if used more than twice daily |
| Ipratropium | Inhaled anticholinergic | None |
| Inhaled corticosteroid (eg, fluticasone, budesonide) | Anti-inflammatory | None |
| Oral corticosteroid (prednisone, methylprednisolone) | Anti-inflammatory | Depression, anxiety, mania, delirium |
| Montelukast tablets or chewable tablets | Possibly both anti-inflammatory and bronchodilator activity | None |
| Theophylline | Anti-inflammatory and respiratory stimulant | Anxiety, especially if blood level is >20 μg/mL |
Ms. P’s mental status alternates between severe anxiety and obtundation. When her anxiety becomes acute, the attending physician prescribes intravenous lorazepam, 1 to 2 mg as needed. Her chart reveals that she has received 4 to 6 mg of lorazepam each day.
A blood test reveals a toxic theophylline level of 20 mg/mL. Acting on the psychiatrist’s suggestion, Ms. P’s physician decreases theophylline to 200 mg/d. Her anxiety improves slightly, but episodes of panic continue to block attempts to wean her from the ventilator. The psychiatrist increases sertraline to 100 mg/d and stops lorazepam. She adds gabapentin, 300 mg every 8 hours.
Within 3 days, Ms. P’s obtundation ceases and she is less tremulous and panicked. She can mouth words and answer questions by nodding. Within 1 week, her anxiety is improved. Five days later, she is weaned from the ventilator. The facility’s psychologist teaches her relaxation, visualization, and breathing exercises to counteract panic and anxiety.
Ms. P is discharged 2 weeks later, after beginning a pulmonary rehabilitation program. Her primary care physician weans her off clonazepam, and her gabapentin and sertraline dosages are continued.
