Olanzapine-induced hyperventilation: case report

Case report

A 30-year-old single male who was diagnosed with schizoaffective disorder according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), had been prescribed various tricyclic antidepressants and selective serotonin reuptake inhibitors in the past, but these were discontinued because, in the patient’s words, “they stopped working.” He then started taking mirtazapine (15 mg at bedtime), which he found to be effective. He was also prescribed typical antipsychotic medications for episodes of paranoia, but these medications were discontinued when symptoms improved. The patient also met the DSM-IV criteria for heroin dependence in full remission. He was enrolled at a local methadone maintenance clinic and was prescribed methadone (110 mg/day). The patient did not have a history of any other psychiatric disorder, but he did have hepatitis C, which he contracted several years earlier, a hip fracture from a car accident 10 years earlier and a benign testicular tumour for which he underwent partial orchiectomy several years earlier. He also had asthma as a child, but it had been stable for several years without ongoing treatment.

During the course of treatment, the patient again began to engage in self-reflective thinking and experience paranoid fears that people were staring at him or constantly thinking and talking about him. He also had persistent, intrusive, negative thoughts about family members having fatal accidents; he reported insomnia due to the intrusive thoughts and complained of being increasingly depressed.

After ruling out other medical or substance-induced causes, various treatment options were explored. The patient continued to take mirtazapine and agreed to start taking the atypical antipsychotic medication olanzapine (5 mg at bedtime). Over the next few days, he reported feeling less paranoid and inquired about increasing the olanzapine dose further. After possible side effects were discussed, the olanzapine dose was increased to 10 mg at bedtime. The patient’s paranoia decreased and his sleep improved, but he continued to have difficulty leaving the house during the day because of excessive fear for his safety. He had not reported any side effects with olanzapine, and, to achieve optimal benefits of the olanzapine, the dosage was increased to 5 mg in the morning and 10 mg at bedtime. Mirtazapine was continued at the same dosage.

The patient continued to do well until the third month of olanzapine therapy when he experienced severe psychosocial stressors, which worsened his paranoia and anxiety. The intrusive thoughts returned, he became increasingly paranoid around people and his sleep deteriorated to about 2–3 hours per night. He reported taking his medications faithfully and denied using any illicit substances. (This was confirmed through drug screening at the methadone clinic.) The dose of olanzapine was increased further to 5 mg in the morning and 15 mg at bedtime. This brought him some relief from insomnia, but he continued to feel anxious and paranoid.

To augment the effects of olanzapine, various other therapeutic options were discussed. The patient agreed to start taking gabapentin (300 mg, 3 times a day), and the mirtazapine was tapered and eventually discontinued. The following week, he reported anxiolytic effects of gabapentin, but the paranoia, social isolation and intrusive thoughts continued. He requested that the dosage of olanzapine be increased again. After a long discussion about the risks and benefits, the dosage of olanzapine was increased to a total of 25 mg/day in divided doses.

The patient responded to the increase, and the improvement continued for 1 week. At that time, he started to complain of sedation and difficulty breathing. Knowing he had a history of childhood asthma, an internal medicine consult was sought. As well, the gabapentin dosage was decreased to 100 mg, twice daily, and 300 mg at bedtime. However, his breathing difficulties, characterized by gasping for air, continued. He also felt very anxious and restless. The patient was advised to go to the emergency room but, when contacted, he said that he felt too paranoid to go to the hospital. Instead, he stopped all his medications and stayed home. He left the house only once the next day to obtain his methadone, and he returned home immediately. Toward the end of the day, he felt that his shortness of breath had improved.

When he returned to the clinic, he suggested that the hyperventilation and breathing difficulty may have been caused by his medications because the symptoms stopped when he stopped taking the medications. However, the paranoia and intrusive thoughts also returned. Because gabapentin was the last medication added to his regimen, it was tapered and discontinued. He resume taking olanzapine at 20 mg/day in divided doses. Another attack of breathing difficulty caused him to stop taking olanzapine again. He became paranoid and was very skeptical of trying a new medication. After a long discussion, he agreed to take olanzapine at a reduced dosage (5 mg twice a day, with an extra dose if needed), but, even at this dosage, he continued to have bouts of breathing difficulty. He found that a lower dosage of olanzapine (5 mg at bedtime) did not cause any difficulty breathing.

The patient described this difficulty breathing or dyspnea as restlessness and a strong urge to breathe heavily. He also experienced chest discomfort and was unable to relax. This feeling would last 8–10 hours.

The patient reluctantly saw his primary care physician, but the physician’s evaluation did not reveal any new medical conditions to account for the hyperventilation and dyspnea. The laboratory test results were as follows: sodium, 143 mmol/L, potassium, 4.2 mmol/L, chloride 98 mmol/L (low), bicarbonate 28.8 mmol/L, calcium 2.47 mmol/L, blood urea nitrogen 4.6 mmol/L UREA, creatinine 88.4 μmol/L, glucose 4.9 mmol/L, globulin 46 g/L, alkaline phosphatase 105 U/L, serum glutamic oxaloacetic transaminase (SGOT) 56 U/L and serum glutamic pyruvic transaminase (SGPT) 93 U/L. His leukocyte count was 9.5 × 10⁶/L, hemoglobin 145 g/L, platelets 237 × 10⁹/L, mean corpuscular volume 93 fL. His thyroid stimulating hormone level was 0.71 mU/L. Hepatitis profile was positive for hepatitis C, with a viral load of 360 000 U/mL. His alpha-feto-protein level was 3.4 μg/L, serum iron level 21 μmol/L and serum iron binding capacity was 62 μmol/L. Test results for autoimmune disorders were negative. Results of chest and abdominal computed tomography and a spirometry evaluation were negative.

After being explained the risks and benefits of various medications, the patient agreed to try risperidone. The initial dosage of 1 mg twice a day was eventually increased to 2 mg twice a day. This reduced his paranoia without causing dyspnea or hyperventilation.