Galantamine may improve attention and speech in schizophrenia

Negative symptoms of schizophrenia that are correlated with cognitive deficits are sometimes refractory to second generation antipsychotics (SGAs) (O’Leary et al., 2000). Neuronal nicotinic acetylcholine receptors (nAChRs) participate in normal cognitive processing (Levin et al., 2005) and there is preliminary evidence that galantamine (a positive allosteric modulator of nAChRs (Maelicke and Albuquerque, 2000)) can improve negative symptoms in Schizophrenia (Allen and McEvoy, 2002; Rosse and Deutsch, 2002). It is thus reasonable to assume that nAChRs may improve cognitive deficits related to negative symptoms as well. In this letter we describe 2 out of 13 patients diagnosed using DSM-IV-TR criteria for schizophrenia and exhibiting prominent negative symptoms at the time of admission. The Scale for the Assessment of Negative Symptoms (SANS) was used to define severity of negative symptoms (i.e., a rating 4 in at least two of the five items of the SANS). Both patients had a negative urine test for metamphetamines and cocaine. One patient was non-adherent to his medication regime, whereas the other was already stable on a SGA and a mood stabilizer. Patient #1 was a 54-year-old caucasian male admitted in June of 2003. He smoked 20 cigarettes a day and he had both disorganized behavior and thinking plus marked paucity of speech. He had been nonadherent to his medication regime (olanzapine) for the last 4 months. This person (as well as the other 11 patients co-treated with galantamine) gave informed consent according to current protocols followed at the Sacramento County Mental Health Treatment Center. Olanzapine was re-started (10 mg/d) and galantamine was added 2 days later (8 mg/d). After the first 7–10 days, the patient exhibited a decrease in total SANS scores (from 86 on admission to 63). At the time of his discharge, 20 days after admission, his thought processes were more organized and he was able to maintain a coherent conversation. Speech and attention showed marked improvements with less gains in anhedonia, affective flattening, avolition or apathy. Patient #2 was a 47-year-old African–American male symptomatically stable on olanzapine (20 mg/d) and divalproex (1500 mg/d). He smoked 5–6 cigarettes a day and was briefly admitted to the hospital in September of 2003 because of behavioral discontrol at his Care home. He had prominent alogia, was unable to perform serial 7’s, and had a SANS score of 96. Galantamine (10 mg/d) was added to his current medications. After 12 days of treatment, a marked improvement in his SANS score (22) was observed. In addition, he was able to verbalize his feelings, was more communicative, and was able to perform serial 7’s. He returned to his Board and Care home. Two years later, patient #2 was re-examined in the outpatient setting. In the intervening period, the galantamine had been discontinued but his earlier medication regimen was maintained. The Screen for Cognitive Impairment in Psychosis (SCIP) (Purdon, 2005) revealed impairment of working memory, new learning, verbal fluency, visuomotor tracking, and delayed recall. Galantamine was again initiated at 8 mg/d. After 34 days the patient showed a remarkable improvement in working memory and delayed recall, though he continued to show impairment in the other examined domains. Negative symptom ratings on the SANS also revealed improvement of attention and speech. Galantamine, used to treat dementia of the Alzheimer’s type (Tariot et al., 2000; Wilcock et al., 2000b), inhibits acetylcholinesterase (AChE), and is a positive allosteric modulator of nAChRs (Maelicke and Albuquerque, 2000). The latter differentiates galantamine from other pure AChE inhibitors (Maelicke and Albuquerque, 2000) such as donepezil which does not have an effect on neither positive nor negative symptoms of schizophrenia (Buchanan et al., 2003). nAchRs, particularly the 7 and the 4 2 subtypes, appear relevant to cognitive processing (Levin et al., 2005). The 4 2 nAchR is the most abundant in the