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Nonantipsychotic Therapy for MonosymptomaticAuditory Hallucinations

To the Editor:

A uditory hallucinations (AH) are commonly encounteredpsychiatric symptoms that are often equated with psycho-sis and prompt antipsychotic prescription. The following

ases describe four psychiatric inpatients and one outpatienthose complaints of “hearing voices” resolved without antipsy-

hotic medication. AH severity was quantified using the Psy-hotic Symptom Rating Scale (1), administered at baseline andfter symptomatic improvement (Table 1).

Case 1. Mr. A was admitted for suicidal ideation and “hearingoices.” He used heroin 4 days earlier, although urine toxicologycreening (UTS) was negative. He described multiple voices comingrom outside his head for the previous 2 years, typically a malerging antisocial behavior or self-harm and a female trying toissuade him. He was started on trazodone 50 mg at bedtimeq.h.s.) and gabapentin (for pain), and after 2 weeks he reportedhat the voices had decreased to quiet, ignorable whispers. At Week, the female voice said, “You know what to do . . . . You do noteed me anymore . . . . Good-bye” and then ceased, without recur-ence. At discharge, Mr. A decided that the male voice was simplyis own thoughts.

Case 2. Mr. B was admitted for “threatening to overdose inesponse to hallucinations” after a recent argument resulting inomelessness. UTS was positive for cannabinoids. Because of hisood symptoms and “hearing voices” for many years, he had been

reated with previous trials of risperidone, olanzapine, lithium,mitriptyline, nefazodone, and trazodone. In the year before admis-ion, he was prescribed sertraline, gabapentin, and quetiapine 300g at bedtime. Although he sometimes described voices as “de-ons” coming from outside of his head, or the voice of his fatherho abused him as a child, he also expressed insight that theseere a product of his own mind. Typically, the voices urged him “too to the dark side” or to kill himself. On rare occasions, he sawead people, such as his brother beckoning him to the afterlife.fter admission, his outpatient regimen was discontinued in favor of

Table 1. Patient’s Age, Previous Diagnoses, Pharmacotherapy, and Treatm

Case Age Previous Chart Diagnoses Pha

1 48 Depressive disorder NOSOpiate, cannabis, alcohol dependence

TrazodoGabape

2 49 Schizophrenia, bipolar disorder, PTSD, mooddisorder NOS

Methamphetamines, opiates, cannabis, alcoholdependence

TrazodoPrazosin

3 52 Major depression, psychotic disorder NOS, “ruleout” schizophrenia

Alcohol dependence

MirtazaTemaze

4 51 Psychotic disorder NOS, “rule out” schizophreniaCocaine dependence

Mirtaza

5 54 Schizophrenia, “rule out” schizophrenia,substance-induced psychotic disorder, majordepression with psychotic features

Cocaine, cannabis dependence

FluoxetTrazodo

NOS, not otherwise specified; PSYRATS, Psychotic Symptom Rating Scale, hdisorder; q.a.m., every morning; q.h.s., at bed time; t.i.d., three times daily.

0006-3223/$36.00Publish

razodone 100 mg q.h.s. and prazosin 1 mg q.h.s. for “nightmares.”ithin 10 days, the voices dissipated, becoming “vague,” brief, and

nfrequent. Prazosin was increased to 3 mg, and at discharge after 14ays, he reported only the occasional nightmare and attributedrevious daytime voices to illicit drug use.

Case 3. Mr. C was treated in the past with fluoxetine forepression and more recent trials of risperidone and loxapineargeting hearing voices since childhood. Throughout his life, heelieved voices to be a “normal” part of his imagination, but inhe past few years, he was diagnosed with schizophrenia. He wasdmitted based on “voices telling me to kill myself” after recentelease from jail, homelessness, and theft of his belongings. Heast used alcohol 3 days earlier, but was not in acute withdrawal.e described voices that were usually inside his head and

muffled,” but during times of distress made statements such as,Watch out, we’re going to get you!” or “You’re going to hurtourself.” Mirtazapine 7.5 mg q.h.s. and temazepam 30 mg q.h.s.s needed for insomnia were started, and after 1 week, the voiceseased. Mirtazapine was increased to 15 mg q.h.s., and uponischarge at 1 month, he denied hearing any voices for therevious several weeks.

Case 4. Mr. D was previously treated with haloperidol,isperidone, and olanzapine based on a 10-year history ofearing voices along a backdrop of chronic cocaine dependence.ollowing a 12-month incarceration without medication, heresented to clinic complaining of “hearing voices” and wastarted on mirtazapine 15 mg q.h.s. He described a single voiceutside his head that made statements such as, “I just saw yourad” or “You’re going to hell.” He stated that the voice wassually “distant” but became more prominent during times oftress, cocaine use, or not taking medications. At 2-week follow-p, he reported complete resolution of the voice.

Case 5. Mr. E had multiple past antipsychotic trials typicallyrompted by psychotic agitation in the setting of chronic illicitrug use. He was admitted after recent release from prison andecause of “command auditory hallucinations” and “suicidaldeation with a plan to jump in front of a train.” UTS was

sponse

therapyBaseline PSYRATS

ScoreEndpoint PSYRATS

ScoreResponse Time

(days)

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34 0 14

0 mg q.h.s.g q.h.s.

32 9 10

5 mg q.h.s.30 mg q.h.s.

29 1 7

5 mg q.h.s. 21 4 14

mg q.a.m.0 mg q.h.s.

27 0 3

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negative. He complained of hearing a voice inside his head thatwas similar to his own thoughts but urging self-harm. The voiceresolved shortly after admission, before initiation of fluoxetineand trazodone for subsyndromal depressive symptoms andinsomnia. At discharge 2 weeks later, he admitted that he liedabout hearing voices and never really experienced AH.

Discussion. These five cases illustrate the ubiquity of“hearing voices” among psychiatric patients at a large metropol-itan Veterans Affairs Hospital, as well as the heterogeneity ofsuch complaints in terms of age of onset and duration, localiza-tion, insight, and beliefs about the voices. All patients shared adiagnosis of substance dependence but claimed persistence ofAH despite periods of sobriety and at the time of evaluation.None had psychotic (e.g., delusions, thought disorder) or ade-quate mood symptoms to warrant a diagnosis of DSM-IV schizo-phrenia or major depression. With only monosymptomatic AH,most had been previously assigned multiple provisional diag-noses of “rule out” schizophrenia, psychotic disorder not other-wise specified, or possible posttraumatic stress disorder.

With the exception of case Number 5, whose malingeredsymptoms disappeared before pharmacotherapy, all patientsexperienced near-complete resolution of hallucinations aftertreatment with a sedating antidepressant. Therapeutic responsewas rapid (3–14 days), although the limited follow-up period(14–30 days) of this anecdotal series precluded longer-termassessment of sustained response. Several potential explanationscould account for the effectiveness of nonantipsychotic interven-tion. First, it is likely that not all experiences described as“hearing voices” represented “true” hallucinations, with abroader differential diagnosis that includes persisting substance-induced psychosis (2,3), nonpsychotic experiences (e.g., depres-sive ruminations, “pseudohallucinations,” or posttraumatic stressdisorder phenomena) (4), and malingering (5). Second, resolu-tion may have been mediated by placebo effects includingremoval of psychosocial stressors, the therapeutic milieu, absti-nence from illicit drugs, and normalization of sleep. Third,previous cases have described potential antidepressant efficacy(whether through nonspecific sedative or specific serotonergic/adrenergic mechanisms) for subtypes of hallucinations (6,7) as

well as “prodromal” psychosis (8). d

www.sobp.org/journal

On the basis of the clinical experience illustrated here, theredictive implications and stigma of a schizophrenia diagnosis,nd the neurologic and metabolic side effects of antipsychoticedications, it is argued that clinicians should be wary of

ssigning a provisional diagnosis of schizophrenia and reflex-vely prescribing antipsychotic medications to patients complain-ng of “hearing voices” in the absence of full diagnostic criteria.ikewise, controlled trials of both antipsychotic medications andonantipsychotic interventions (e.g., antidepressants, benzodiaz-pines, sedating antihistamines, psychotherapy) in such patientsho “hear voices” is warranted to better elucidate the safest andost effective interventions for monosymptomatic AH.

Joseph M. Pierre

A West Los Angeles Healthcare Center1301 Wilshire Boulevard Building 210os Angeles, CA 90073

The author reports no biomedical financial interests or po-ential conflicts of interest.

. Haddock G, McCarron J, Tarrier N, Faragher EB (1999): Scales to measuredimensions of hallucinations and delusions: The psychotic symptomrating scales (PSYRATS). Psychol Med 29:879 – 889.

. Glass IB (1989): Alcoholic hallucinosis: A psychiatric enigma—1. The de-velopment of the idea. Br J Addict 84:29 – 41.

. Pihlgren EM, Boutros NN (2007): Psychostimulant-induced chronicschizophrenia-like disorder. Clin Schizophr Relat Psychoses 1:54 – 63.

. Pierre JM (2010): Hallucinations in nonpsychotic disorders: Toward adifferential diagnosis of “hearing voices.” Harv Rev Psychiatry 18:22–35.

. Pierre JM, Wirshing DA, Wirshing WC (2003): “Iatrogenic malingering” inVA substance abuse treatment. Psychiatr Serv 54:253–254.

. Stephane M, Polis I, Barton SN (2001): A subtype of auditory verbalhallucinations responds to fluvoxamine. J Neuropsychiatr Clin Neurosci13:425– 427.

. Koethe D, Dietl T, Leweke FM, Friess E (2007): Cessation of complex visualhallucinations during treatment with mirtazapine. Pharmacopsychiatry40:82– 87.

. Cornblatt BA (2002): The New York high risk project to the Hillsiderecognition and prevention (RAP) program. Am J Med Genet 114:956 –966.

oi:10.1016/j.biopsych.2010.04.026