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Pharmacopsychiatry 2007; 40(2): 82-83
DOI: 10.1055/s-2007-961818
Letter

© Georg Thieme Verlag KG Stuttgart · New York

Cessation of Complex Visual Hallucinations during Treatment with Mirtazapine

D. Koethe 1 , T. Dietl 2 , F. M. Leweke 1 , E. Friess 2
  • 1Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany
  • 2Max-Planck-Institute of Psychiatry, Munich, Germany
Further Information
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Correspondence

D. KoetheM.D. 

Department of Psychiatry and Psychotherapy

University of Cologne

Kerpener Str. 62

50924 Cologne

Germany

Phone: +49/221/478 86 23 1

Fax: +49/221/478 87 20 0

Email: koethe@ecnp.net

Publication History

received 21. 8. 2006 revised 10. 12. 2006

accepted 15. 12. 2006

Publication Date:
19 April 2007 (online)

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Table of Contents #

Introduction

Hallucinations are one of the hallmarks of psychotic disorder. However, the occurrence of visual hallucinations in particular is not confined to idiopathic psychiatric disorder as schizophrenia, but is also frequently encountered in neurological and metabolic disorders affecting brain function. Medical conditions associated with visual hallucinations are focal epilepsy (mainly temporal lobe epilepsy), Lewy body disease, and the Charles Bonnet syndrome in patients with impaired vision or alcohol withdrawal. Unfortunately, well-designed randomized controlled clinical trials regarding the treatment of visual hallucinations associated with various disorders are scarce [6] [7]. Treatment of visual hallucinations is generally considered a difficult issue. Dopamine-blocking agents are the mainstay of symptomatic pharmacological treatment in many cases of hallucinosis where treatment of the underlying medical cause does not result in rapid and sufficient improvement of hallucinations. Non-antidopaminergic treatment strategies for visual hallucinations are of clinical importance because first, not all patients with visual hallucinations respond to dopamine-blocking agents satisfactorily and, second, this treatment is not indicated under certain conditions, e.g., in Lewy body dementia.

Here, we report two cases with complex visual hallucinations of unknown origin. These patients were treated with mirtazapine for a depressive syndrome. Both patients experienced a cessation of the visual hallucinations shortly after the onset of mirtazapine treatment.

In the first case, a 54-year-old woman was admitted to hospital because of treatment-resistant chronic visual and acoustic hallucinations, which she had been having for two years and depressive symptoms (HAMD-21 score on admission: 26). She had a history of meningoencephalitis at the age of five. Additionally, she suffered from ovarian cancer in 1979 without any metastases up to the time of admission and a dietary treated diabetes mellitus (HbA1c 6.1%). Laboratory blood and CSF parameters were all normal except slightly elevated levels for serum sodium (146 mmol/l) and serum triglycerides (207 mg/dl). Blood pressure, hydration and medical examination were normal.

She had several episodes featuring loss of concentration, delusions and dysphoria, and two years prior to admission she had additionally suffered from visual and acoustic hallucinations. She reported seeing spiders and cats in her flat, and men suddenly appearing behind her. The hallucinations lasted for minutes, occurred several times a day and were not associated with any motor seizure activity. She had developed delusions as she thought the men, appearing in her hallucinations, were threatening her. She developed severe depression and was unable to work. Previous admissions and treatment with haloperidol (12 mg/day) and maprotiline (150 mg/day) resulted in improvement in mood and drive, but not in a reduction of hallucinations. A cranial CT scan showed a 5 mm hypodensity at the right basal ganglia. EEG showed intermittent background slowing without any evidence for epileptiform activity. Because of the limited efficacy, we discontinued haloperidol and maprotiline. We administered antidepressants as the patient showed a depression with marked slowing of psychomotor. Treatment with up to 45 mg of mirtazapine per day unexpectedly resulted in complete and persisting cessation of the hallucinations within days.

After the hallucinations had disappeared, she still suffered episodic anxiety, which was differentially diagnosed as a seizure equivalent; therefore a co-medication of oxcarbazepine of up to 1500 mg/day was given. The patient could be discharged after six weeks, clearly improved in mood and anxiety symptoms (HAMD-21 score on discharge: 13).

In the second case, a 78-year-old woman with a previous history of breast cancer at the age of 40, elevated blood pressure, hyperlipidemia and COPD (chronic obstructive pulmonary disease) was admitted to hospital because of episodes of complex visual hallucinations. She perceived moving chess figures superimposed on moving people. Hallucinations were accompanied by fear, depressive mood and affective instability (HAMD-21 score on admission: 23). The hallucinations lasted for minutes, occurred several times a day and were not associated with additional neurological symptoms suggestive for epileptic disorder. She reported that weeks ago she was hit by a barrier on her right temple and lost consciousness for few minutes. The EEG showed intermittent bi-frontal sharp-wave activity with an accentuation of the right side, which normalized in a follow-up EEG. Cerebral MRI revealed discrete lesions of the basal ganglia and two small cysts (left fronto-parietal and right dorsal in the cerebellum). Laboratory blood and CSF parameters were all normal except elevated levels for cholesterol (293 mg/dl) and homocysteine (15.6 mol/l) (including tumor and immunological markers). Blood pressure at admission was 160/85 mmHg, medical examination were normal. The patient was never treated for psychiatric reasons before, but due to sleep disturbance she was taking a stable dose of zolpidem (10 mg/day) for the last two years. Additionally she was taking cerivastatin, losartan, hydrochlorothiazide and metoprolol.

Because of the depressed mood, affective instability and insomnia, a monotherapy with mirtazapine of up to 30 mg/day was started. Within days, the patient reported markedly reduced hallucinations, which only occurred in the evening and disappeared when she changed her activity. Subsequently she improved in mood and anxiety as well and reported a better sleep quality (HAMD-21 score on discharge: 11); therefore zolpidem could be tapered out easily. Within three weeks the patient was discharged without any hallucinations.

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Discussion

Visual hallucinations have several etiologies and are associated with a variety of disorders. As visual hallucinations are usually difficult to treat, identification of the underlying disorder or cause is necessary to determine the appropriate treatment, which should be directed at that disorder or etiology. In the cases presented above, the clinical and laboratory-chemical investigations were not suggestive of a somatic genesis, the described neuroradiological lesions were not etiologically relevant for the visual hallucinations and most findings were according to age.

As an antidepressive treatment was required in both patients, we chose mirtazapine in the second case on the basis of our experience from the first case, where mirtazapine displayed beneficial effects on visual hallucinations in addition to its efficacy in depression. Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin but acts as an antagonist at presynaptic alpha(2)-receptors, at histaminergic H1 receptors and at postsynaptic 5-HT2 and 5-HT3 receptors, leading to a more extensive stimulation of 5-HT1 receptors. Furthermore, mirtazapine has been shown to acutely inhibit cortisol secretion in healthy subjects.

The major pharmacological effect for the cessation of visual hallucinations might be the blocking of 5-HT2A receptors, because an involvement of the 5-HT2A receptor system in the pathogenesis of visual hallucination has been postulated from clinical and pharmacological data [2] [4].

It has been suggested that atypical neuroleptics like clozapine exert their antihallucinatory action by blocking 5-HT2A-receptor signaling in addition to its antidopaminergic effects. Therefore, the hyperactivity of serotonergic neurotransmission was suggested as a relevant factor for at least some symptoms of schizophrenia [1]. Complex visual phenomena in migraine can be blocked as well by 5-HT2 antagonists such as pizotifen and methysergide, but not by 5-HT1 agonists like sumatriptan [5]. Furthermore, it has been shown that the hallucinogenic potency of LSD (lysergic acid diethylamide) strongly correlates with its in vitro 5-HT2-receptor binding affinities in rat and human brain. Gouzoulis-Mayfrank et al [3]. reported about the serotonergic hallucinogen N,N-dimethyltryptamine (DMT), a 5-HT2A agonist whose hallucinogenic effects were similar to the antiglutamatergic hallucinogen (S)-ketamine. Thereby, phenomena that resemble positive symptoms of schizophrenia were more pronounced after DMT, and in particular visual phenomena. These studies imply that treatment with 5-HT2-receptor antagonists may be effective in reversing visual hallucinations [8]. Siddiqui et al. [9] reported a case of Charles Bonnet Syndrome whose visual hallucinations remitted within the next three days after treatment with a dose of 7.5 mg/day of mirtazapine had been started. In this reported case a very low dose of mirtazapine was effective.

Therefore, we raise the question whether mirtazapine, by blockade of 5-HT2A neurotransmission, had contributed to the unexpected cessation of the visual hallucinations in the cases mentioned above. This would support the hypothesis that this drug can interfere with higher-level visual processes via modulation of 5-HT2A receptors.

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References

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Correspondence

D. KoetheM.D. 

Department of Psychiatry and Psychotherapy

University of Cologne

Kerpener Str. 62

50924 Cologne

Germany

Phone: +49/221/478 86 23 1

Fax: +49/221/478 87 20 0

Email: koethe@ecnp.net

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References

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Correspondence

D. KoetheM.D. 

Department of Psychiatry and Psychotherapy

University of Cologne

Kerpener Str. 62

50924 Cologne

Germany

Phone: +49/221/478 86 23 1

Fax: +49/221/478 87 20 0

Email: koethe@ecnp.net

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