A Subtype of Auditory Verbal Hallucinations Responds to Fluvoxamine

SIR: Auditory verbal hallucinations (AVH) involve the perception of speech in the auditory modality without corresponding external stimuli. Their pathophysiology is not clear, and they may not have a uniform etiology. AVH are encountered in many psychiatric, neurological, and substance abuse disorders. They vary phenomenologically along multiple dimensions, such as the presence or absence of insight into the abnormal nature of the hallucinations, sensory clarity, location in the inner or outer space, concomitancy or not to normal external stimuli, and repetitive versus systematized content.^1–5

It is theorized⁶ that the speech perception area (Wernicke's area) constitutes the final common pathway for experiencing AVH and that the hallucinatory pathology involves a distributed neural network. The phenomenological variations are thought to reflect variability in the underlying neuropathology⁷ (possibly in the location of the pathology along the distributed neural network). If this is the case, AVH with different characteristics could respond to different pharmacological agents. In the following case reports we show that AVH with repetitive and fixed content responded to treatment with the antiobsessional agent fluvoxamine.

Case Reports

Case 1. A 44-year-old white male was admitted to the Psychiatric Partial Hospital (PPH) at the Minneapolis Veterans Affairs Medical Center for exacerbation of psychotic and depressive symptoms. He is single, without children, unemployed, and was living in a low-intensity assisted living facility for 1 year prior to admission. He was raised by his parents and was described as an average student, shy and socially withdrawn. He completed high school and vocational school and had 3 years service in the navy. After discharge from the military, he held minor part-time jobs and lived at his mother's house, continuing to live there 3 years after her death. He was transferred afterwards to sheltered living because of his difficulties functioning on his own.

The patient's 11-year psychiatric history was marked by multiple exacerbations and remissions. The symptoms included depressive mood, difficulty taking care of himself, poor hygiene and grooming, low energy, lack of motivation, feelings of hopelessness, helplessness, and worthlessness, poor concentration, decision-making difficulties, social withdrawal, dependency on his family, frequent suicidal ideation without suicide attempts, and hearing “voices.” He reported hearing one voice asking him to hang himself. The “voice” had clear acoustic qualities and variable loudness. It was triggered by going into the bathroom and always had the same repetitive content: “Do it, hang yourself in the bathroom.” The patient did not resist the occurrence of these voices and attributed them to the devil.

On admission, the patient was symptomatic on therapeutic doses of divalproex and lithium, risperidone, sertraline, bupropion, and zolpidem. Risperidone and sertraline were increased to daily doses of 8 mg and 250 mg, respectively. No improvement was noted in 4 weeks, and the patient was a candidate for electroconvulsive therapy. Given the obsessional repetitive content of his AVH, the patient was started on fluvoxamine, which was progressively increased to 150 mg daily. Within a week from the initiation of fluvoxamine, the patient reported a decrease in his AVH and improvement in his socialization: “It seems it is easier for people to be around me.” AVH stopped after 3 weeks, and the patient had sustained improvement in mood, affect, grooming, hygiene, and social interactions. Both bupropion and divalproex were discontinued without relapse. At 8 weeks, symptoms were still remitted.

Case 2. A 49-year-old black male was referred to the PPH after an inpatient stay in relation to worsening of depressive and psychotic symptoms and suicidal risk. He is a Vietnam veteran, single, and the father of two children who live with their mother. He was raised by his parents, graduated from high school, and joined the Navy for 3 years. He was raped around age 8 by people unknown to him. His longest job (as firefighter) lasted 7 years, but in recent years he has supported himself mostly by working odd jobs.

His psychiatric history was significant for late onset of cocaine abuse (at age 37) and at least 8 years' history of fluctuating mental illness. The symptoms included depressed mood, decreased appetite, disturbed sleep, loss of libido, concentration difficulty, suicidal ideation, and hearing “voices.” His hallucinations had the following characteristics: two male voices, repetitive content (“It is time to go, it is time to leave”), located externally, deep and muffled, and almost constant. He would struggle against their occurrence, and at times would give up: “I jump on a freight train and leave.” This resulted in remittance of the voices. He attributed these hallucinations to “being possessed by the demons.” He said he spent the last 8 years traveling around the country, staying 1 to 8 months at each place. He had had irregular psychiatric treatment with different antipsychotics, antidepressants, and mood stabilizers without benefit. Records from previous hospitalizations showed similar presentations.

We treated this patient with a combination of risperidone (3 mg/day) and fluvoxamine (up to 200 mg/day). A significant improvement of his symptoms was noted for at least 2 months, and he was able to find a job and an apartment. At a follow-up 4 months after initiating treatment, the patient reported that he had stopped fluvoxamine (but not risperidone) a month earlier because of concerns about side effects. He was depressed but not suicidal. He was experiencing hallucinations with the same characteristics as before and was planning to leave town. To our knowledge, the only time this patient experienced relief from hallucinations was when he was on fluvoxamine.

Comment

AVH that have repetitive and fixed content can be contrasted to AVH that have a systematized and rich content. Claude and Ey¹ relate the first category to an obsessional subgroup of hallucinations (état obssessionel passif). We are not aware of evidence in the literature that such hallucinations would respond to treatment with antiobsessional agents, and currently there is no cognitively or biologically validated subgrouping of AVH.

Nonetheless, it has long been known that some of the phenomenological variables of AVH correspond to specific neural substrates. For example, anosognosia (lack of awareness of the abnormal nature of a symptom) corresponds to symptom-specific brain lesions: the visual associative cortex in the case of Anton syndrome (blindness associated with unawareness of being blind),⁸ and the nondominant hemisphere in the case of anosognosia of hemiplegia.⁹ Similarly, in a positron emission tomography study, verbal obsessive stimulations, compared with neutral stimulations, are associated with activation of the orbitofrontal regions.¹⁰ If there are differences in the neural substrate when patients are aware or not of the pathological nature of their hallucinations, or if they have hallucinations with repetitive versus systematized content, the treatment of AVH could vary accordingly.

These two patients suffer from AVH with repetitive content. The first patient was passive to their occurrence; the second resisted it. Both patients were not responsive to treatment with multiple antipsychotic and antidepressant medications. Fluvoxamine, an established antiobsessional agent,¹¹ decreased and stopped AVH in both cases. This response could be related to direct or augmenting effect of fluvoxamine on AVH. The treatment response was not limited to AVH but extended to other aspects such as mood and affect. This could be due to improvement of AVH and/or direct effect of fluvoxamine on mood and affect.

Evidence from two patients is not enough to draw definitive conclusions about the effect of fluvoxamine in this subgroup of AVH and the pathological significance of such effect. However, since approximately 50% of hallucinating patients with psychotic spectrum disorders experience AVH with repetitive content (manuscript in preparation), clinical trials may be worthwhile.