Pharmacological treatment of frontotemporal dementia: treatment response to the MAO‐A inhibitor moclobemide

No proven psychopharmacological therapy has been established so far for frontotemporal dementia (FTD) and the respective literature is made up by case reports and case series. Acetylcholinesterase inhibiting drugs generally have not been found useful and may even enhance irritability and aggressiveness. Most studies reporting therapeutic benefit were conducted with serotonin reuptake inhibitors (SSRIs). Anderson et al. (1995) described two cases of FTD with depression, who responded to treatment with paroxetine and lithium. Swartz et al. (1997) found that in 11 subjects with FTD treated with SSRIs, disinhibition was improved in six out of nine patients, carbohydrate craving in five out of nine patients and compulsions in four out of seven patients. Moretti et al. (2003) observed in eight FTD patients treated with paroxetine an overall reduction of behavioral symptoms and a decrease of caregiver stress. As there is evidence for both a serotonergic and a dopaminergic deficit in FTD, a therapeutic trial with a MAO-A inhibitor seems to be justified. In a previous report on the effects of selegiline in FTD, an improvement of behavior and a renewed interest for different aspects of life have been reported (Moretti et al., 2002). Moclobemide, a selective and reversible MAO-A inhibitor, may be particularly suited, because it has been found useful for the treatment of depression in dementia and it has no anticholinergic properties. Thus, we studied the effects of moclobemide treatment in an open case series of six patients with FTD. The patients (five men and one woman, aged between 57 and 67 years; mean: 62 years) were admitted to the Day-Clinic for the Elderly at the Central Institute of Mental Health in Mannheim or to the Department of Geriatric Psychiatry at Schwerin (GG). Diagnosis of FTD was made according to the clinical criteria formulated by McKhann et al. (2001). The clinical symptoms of the patients are presented in Table 1. Age at onset of symptoms was between 51 and 62 years (mean: 57 years). MRI scan revealed predominantly left fronto-temporal atrophy in three patients (ES, WW, GG), symmetrical atrophy of the temporal lobes (KK), predominantly right temporal atrophy (RB) and no atrophy (EW) in one patient respectively. Family history was obtained in five subjects and was positive in one subject (ES), probably for FTD in a second-degree relative. EEG was found to be normal in five patients; in one (KK) there was a slight, generalized increase of slow-wave activity. Cerebrospinal fluid (CSF) was studied in four subjects, revealing slightly increased albumine concentrations in two of them (KK, RB). In one patient (WW) a brain biopsy had been performed with the finding of large amounts of Pick bodies within the right temporal cortex. All patients were treated with moclobemide at dosages between 300 and 600 mg daily for four weeks. Under moclobemide treatment, improvements were observed with respect to symptoms and impairments in various domains, mainly in affect, behavior and speech. The psychopathological symptoms and their changes under moclobemide treatment are summarized in Table 1. Depressive symptoms were reduced in three patients in which they initially were present; aggressive behavior or irritability were alleviated in four out of five patients, in one it was