Introduction
The Charles Bonnet syndrome (CBS) is usually characterized by complex visual hallucinations (distinct figures such as animals or faces) and ocularpathology causing vision loss. Two other accepted characteristics are an insight into the unreality of perceptions and the absence of psychiatric morbidity (Tueth et al., Reference Tueth, Cheong and Samander1995; Rovner, Reference Rovner2006).
Once considered rare, reports of CBS are increasing as the population ages and the prevalence of vision disorders (such as age-related macular degeneration, glaucoma, and cataracts) increases (Schadlu et al., Reference Schadlu, Schadlu and Shepherd2009). Sensory deprivation due to peripheral damage in CBS probably removes competition with endogenous representation – imagination – and thus lowers the threshold for hallucination (Braun et al., Reference Braun, Dumont, Duval, Hamel-Hébert and Godbout2003). Imaging studies demonstrate that when elderly individuals suffer from an eye disease, subsequent excessive cortical compensation in the lateral temporal cortex, striatum, and thalamus may precipitate the development of visual hallucinations (Adachi et al., Reference Adachi, Watanabe, Matsuda and Onuma2000).
Several case reports suggest that pharmacologic agents can be effective in the alleviation of hallucinations associated with CBS. Typical and atypical antipsychotic drugs as well as cholinesterase inhibitors, antiepileptics, and a variety of antidepressants have all been anecdotally reported in the literature (Paulig and Mentrup, Reference Paulig and Mentrup2001; Maeda et al., Reference Maeda, Shirayama, Nukina, Yoshioka and Kawahara2003; Schadlu et al., Reference Schadlu, Schadlu and Shepherd2009). Recently, Lang and colleagues (Reference Lang2007) reported the first case to show that selective serotonin (and noradrenaline) reuptake inhibitors maybe an effective and well-tolerated treatment for visual hallucinations associated with vision loss. They described the case of an l8-year-old woman, who was hospitalized after long mild depressive symptomatology. For one year she experienced daily sudden, unexpected, vivid, and elaborate hallucinations; insight was completely present and she understood that hallucinations were due to her vision loss. No cognitive impairment was reported. The visual acuity was hand motion. After four days of treatment with venlafaxine the hallucinations completely disappeared. This report adds to evidence implicating serotonergic pathways in the pathogenesis of visual hallucinations.
To date there have been no reports of treatment strategies for patients suffering from CBS who are unresponsive to antipsychotic drugs. This report describes consecutive CBS patients who were treated with a selective serotonin reuptake inhibitor (SSRI; escitalopram) after failure of antipsychotic treatment.
Methods
A retrospective analysis of computerized medical charts of elderly patients treated at our center from January 2010 to December 2011 was undertaken. Patients, referred to one of the authors after “failing” to respond to an antipsychotic, were offered a trial with escitalopram. This was not a research project. The data were analyzed retrospectively following approval of the local Institutional Review Board (IRB). The Tirat HaCarmel mental health center is a university-affiliated tertiary care center serving the urban catchment area of greater Haifa with approximately 500,000 persons.
Elderly patients with complex visual hallucinosis who were treated at our center from January 2010 to December 2011 were included in the study according to the following criteria: (1) aged 65 years and older, (2) patients who had been unsuccessfully treated for CBS with at least one antipsychotic during the current episode, (3) severity of CBS necessitating further treatment, (4) normal brain CT, and (5) score of ≥27 on the Mini-Mental State Examination (MMSE; Folstein et al., Reference Folstein, Folstein and McHugh1975).
Previous antipsychotic treatment was administered for a minimum period of eight weeks as follows: haloperidol 2.5 mg/daily in two patients, perphenazine 8 mg/daily in two patients, and risperidone 2mg/daily in four patients. In the majority of patients side effects were reported during antipsychotic treatment. In 6/8 patients extra-pyramidal side effects were noted.
Outcome measures
The Clinical Global Impression scale (CGI; Guy, Reference Guy1976) is a scale used to assess treatment response in psychiatric patients. Severity was rated on a seven-point scale (1 = normal to 7 = extremely ill), and improvement was also rated on a seven-point scale (1 = very much improved to 7 = very much worse). Change in the CGI-severity was defined as a primary outcome in the present study.
Results
There were ten patients suffering from CBS unresponsive to antipsychotics. However, in two cases patients stopped antipsychotic treatment in less than two weeks and so are not included in the present series. Thus, during the study period eight patients suffering from CBS unresponsive to antipsychotic drugs were offered a switch to escitalopram treatment. There were four men and four women, with a mean age of 81.7 ± 7.3 years (range: 76–88 years). All had been diagnosed as suffering from cataract – in 5/8 patients cataract was bilateral. Comorbid physical conditions were common with 7/8 patients suffering from hypertension, 3/8 suffering from ischemic heart disease, 3/8 suffering from diabetes, and 2/8 suffering from chronic obstructive pulmonary disease (COPD). Hallucinations were present for a mean period of 10.7 + 5.3 months prior to escitalopram treatment.
Brain CT imaging was normal in all the patients. In one patient an incidental finding of a small frontal meningioma was demonstrated – judged by a neuroradiologist as of no clinical significance. All patients were scored on the MMSE by the treating physician (Yoseph Bergman) and all had an MMSE total score of ≥27/30 (Folstein et al., Reference Folstein, Folstein and McHugh1975).
None of the patients had reported improvement with antipsychotic treatment. Mean CGI-severity upon switching to escitalopram treatment was 5.7. This was significantly reduced to 1.8 (p < 0.001) after eight weeks of escitalopram treatment. All patients had improved. The baseline versus eight weeks CGI-severity scores were as follows: 6 to 2, 6 to 2, 6 to 3, 5 to 3, 6 to 1, 5 to 2, 6 to 2, and 6 to 1.
Correspondingly, mean CGI-improvement score after eight weeks of escitalopram treatment was 1.9. The mean escitalopram dose was 11.8 mg/daily (range: 10–15 mg). All patients tolerated the treatment well with no side effects, nor any adverse events were reported.
Discussion
Antipsychotics are frequently used to treat psychosis in elderly patients, but safety warnings abound. Escitalopram was recently compared with risperidone by our group for psychotic symptoms associated with Alzheimer's disease. There were no adverse events in the escitalopram group, whereas escitalopram and risperidone did not differ in efficacy in reducing psychotic symptoms in elderly patients with Alzheimer's disease (Barak et al., Reference Barak, Plopski, Tadger and Paleacu2011). These encouraging results together with a report of Lang et al. (Reference Lang2007) of the first case to show that SSRIs maybe an effective and well-tolerated treatment for visual hallucinations associated with vision loss led to the present series of CBS patients being treated with escitalopram. The response in our patients was uniformly good and tolerability was excellent.
Antipsychotic medications are habitually prescribed for the treatment of CBS because these are indicated to treat delusions and hallucinations in schizophrenia. Their efficacy in CBS has not been established in clinical trials (Coletti Moja et al., Reference Coletti Moja, Milano, Gasverde, Gianelli and Giordana2005). If one is to take CBS as a benign example of post-lesion hallucinosis, we must concur with Batra and colleagues (Reference Batra, Bartels and Wormstall1997) that few successful methods of treatment have been described. Therapies with classic neuroleptics, antidepressants, or benzodiazepines have been generally found to be unpromising, improvement resulting from anticonvulsant treatment has been observed in a few cases, and single case report demonstrates successful treatment of CBS with cholinesterase inhibitor donepezil (Batra et al., Reference Batra, Bartels and Wormstall1997; Burke et al., Reference Burke, Roccaforte and Wengel1999).
The use of escitalopram in the present series is unique in that patients treated had been unresponsive to exposure to standard antipsychotic medication. However, the limitations of the present report need be mentioned: retrospective design, sample size is small, patients were selected from a specific catchment area, and follow-up duration is relatively short. It is important to note that dose–response association with a modest QTc prolongation was identified for citalopram and escitalopram but not for other antidepressants examined in a large cross-sectional study of electronic health records in the United Kingdom (Castro et al., Reference Castro2013).
In conclusion, the aging of the population will result in CBS becoming more prevalent, and thus all physicians who care for low vision or elderly patients should be aware of its clinical features and treatment alternatives. Further exploration of treatment options will be necessary. The positive outcome of this case-series warrants further evaluation of escitalopram as an agent for psychotic conditions in elderly patients.
Conflict of interest
None.
Description of authors’ roles
Dr Bergman was the treating physician. He designed this study. Prof Barak consulted on treatment. Both wrote the manuscript.
