Abstract
Olanzapine, a serotonin–dopamine antagonist, is widely regarded as a safe and efficacious antipsychotic drug. Haemodynamic side-effects such as bradyarrhythmic shock have rarely been associated with olanzapine. We report a case of olanzapine-induced bradyarrhythmic shock in a patient who had no history of physical illness.
A 62-year-old Taiwan man was admitted to the psychiatric ward of Tsyr-Huey teaching Mental Hospital with a relapse of schizophrenia with nihilistic delusion, disorganized behaviour, and parkinsonism side-effects. He had been on clothiapine (40 mg day−1) and propranol (30 mg day−1) in partial remission for more than 24 months. In our ward, his treatment was immediately switched to olanzapine, 10 mg day−1, and trihexylphenidyl, 6 mg day−1. His psychiatric history included paranoid schizophrenia of 34 years duration, three admissions, and trials of different regimens of antipsychotics such as haloperidol, sulpiride, flupenthixol, and chlorpromazine. He had no history of physical illness including cardiovascular diseases.
One week later, his dosage of olanzapine was increased to 15 mg day−1 and trihexylphenidyl was stopped because his parkinsonism ceased. The next day, he developed a pale expression, cold sweating, hypotension (blood pressure (BP) 80/60 mmHg), and bradycardia (heart rate (HR) 52 b.p.m.). Because of cardiac side-effects and confusion, he was immediately referred to the intensive care unit. A 12-lead electrocardiogram showed sinus bradycardia at 48 b.p.m., biphasic T wave, and a prolonged QTc interval of 503 ms. All laboratory values and studies produced normal results. Intravenous fluids and atropine were administered after olanzapine was withdrawn. Two days later his condition improved (BP 104/69 mmHg; HR 62 b.p.m.) and his consciousness gradually cleared. Subsequently, he was returned to the psychiatric ward.
Two weeks after olanzapine was discontinued, he was started on risperidone 1 mg day−1, which was gradually increased to 3.5 mg day−1 for the next 1 month. After more than 6 months of follow up, he experienced no side-effects but still had nihilistic delusion.
A MEDLINE search revealed only three published reports of olanzapine as the sole cause of bradyarrhythmia. In the first case report, a patient underwent bradycardiac shock with severe intoxication probably from olanzapine [1]. Other case reports suggest that rapidly rising olanzapine plasma concentrations may be associated with the side-effects of hypotension accompanied with bradycardia [2]. Another case study reported that an 84-year-old man with Alzheimer's dementia underwent olanzapine-induced bradycardia without shock [3]. This emphasizes that old age, as with the present patient, may exaggerate the adverse effects of olanzapine. We emphasize that patients such as the present one, without any history of a heart problem, require more careful monitoring, especially during initial use of olanzapine at high dosage.
Economic analyses of the cost-effectiveness of treating people with mental disorders such as that recently published in he Journal [1] are increasingly important as psychiatrists battle for a slice of health-care budgets.
Neglecting such economic perspectives is no longer tenable specifically for psychiatry compared to the rest of medicine. For example in the USA, traditionally regarded as a heartland for psychiatry, harsh economic winds are blowing that are likely to be felt elsewhere in the world shortly. Recent changes in the payment for mental health services in North America are predicted to lead, over the next few years, to a decrease in the number of psychiatrists, plummeting from about 30 000 full-time equivalent physicians at present to between 11 000 and 18 000 [2, 3].
However, such analyses can run the risk of simplifying the problem of mental health at a public health level to such a degree as to invite disregard by policy-makers.
For example, the concepts of ‘years lived with disability’ and ‘disability weight’ as operationalized into the key variables used in the recent study by Andrews are frequently problematic [1]. They, and similar quality of life measures, are often derived from the arena of physical health. They may as a result emphasize personal physical disability and distress linked to present symptoms [4]. Key burdens of psychiatric disorder, which are frequently underestimated by sufferers, are the various profound and/or subtle long-term social disabilities they produce [4]. These can transform life pathways to produce social isolation, unemployment and/or underemployment long after the symptoms of an illness have ostensibly disappeared.
If these wider social disabilities are taken into account it is possible that disability measures might jump in scale when psychiatric disorders are considered, rendering cost-effective analyses even more favourable towards the treatment of mental illness.
But even if this were so, Andrews’ analysis would still be problematic because it neglects the fundamental problem that while patients gain from any increased spend generated by such a cost-effective analysis, it is the State or third-party payer that bears the financial burden up front and reaps any economic benefit only in years to come, long after the government has been penalized by an electorate for the contingent tax rises.
Electorates ultimately have to bear these costs and the question thus arises: cost-effective for whom? Is it really ‘cost-effective’ for all those who have to pay for the mental health of a minority of the population?
All health-care systems arise out of and reflect a value system derived from the society in which they are based. Andrews points out that the proportion suffering from various forms of mental illness who are actually receiving treatment is often minute in contrast with that fraction of those burdened with physical problems obtaining medical help [1].
The gap between physical and mental health must reflect wider cultural attitudes that would need to change before better provision could have any impact or make meaningful sense to the payers.
This is likely to be much more complex for psychiatry than for the rest of medicine: educating the public about diabetes in order to dispel ignorance about the disorder is a tall order but itself is trifling in comparison to the undertaking of transforming lay attitudes to psychiatric disorder. Psychiatry challenges popular notions around personal responsibility and will when it diagnoses the ‘victims’ of alcoholism and ‘impulse control disorders’ [2].
Also, few of those bearing health-care costs are likely to be enthusiastic about elevating previously dormant demand by funding better care. The more people are encouraged to come forward to receive treatment now available (because they are the victims of ‘alcoholism’), the larger the pent-up previously unmeasured demand is likely to be unleashed, creating a ‘bottomless well’ effect that difficulty in obtaining treatment effectively helps to keep pent up. And usefully so, as far as many stretched health-care systems are concerned.
Finally, is it not likely that the best long-run health status per dollar spent on head of population is not indeed spending on psychiatric or medical care or treatment, as many cost-effectiveness studies persist in focusing on; but instead spending prevention (e.g. anti-smoking, anti-obesity and improved coping skills) leading to less psychiatric disorder in the face of adversity or stress.
Relying on cost-effectiveness analyses is unlikely to be persuasive if the most effective medical approach continues to be resolutely ignored by mainstream psychiatry: prevention.
After many years specializing in the treatment of depression, and based on my clinical observations, I suggest that the acronym YES (yawning, expressive dysphasia, and silly mistakes) describes an underrecognized syndrome, when antidepressants have eliminated many symptoms of depression and anxiety. Having fewer symptoms left to combat, it seems that antidepressants then adversely affect the patient's general neuropsychological functioning and cognition.
Subjectively, patients may report a fear that their previously improving depressive illness is relapsing, as they notice deterioration in their energy levels, concentration, memory and general functioning. Sedation, yawning, clumsiness and drowsiness are associated with difficulty finding the right word when thinking or talking. Simple errors in spelling, calculation or typing speed and accuracy occur, and objects may be put in the wrong place (such as putting sugar in the refrigerator).
Failure of the antidepressant, described in the literature as antidepressant ‘poop-out’, may be suspected, with consideration of the need to abandon a previously effective antidepressant. But, on questioning, patients may recognize that this is a qualitatively different sensation to the sensation of their original depressive illness.
This overshoot syndrome responds within days to a slight reduction in antidepressant dosage. Simple dosage titration avoids considerable disability and distress in unnecessary antidepressant changeover.
This clinical observation has widespread application potentially. I suggest that teaching patients to increase their antidepressant dosage during symptom relapse, and to reduce their dosage during antidepressant overshoot, will improve management of depression, improve long-term compliance, and assist in our aim of achieving faster and full remission of depressive illness.