A Randomized Clinical Trial of Oxytocin or Galantamine for the Treatment of Negative Symptoms and Cognitive Impairments in People With Schizophrenia

Abstract

Purpose/Background Negative symptoms and cognitive impairments tend to co-occur in people with schizophrenia. If their association with each other is due, in part, to shared pathophysiology, then this suggests that a single drug could potentially be effective for both domains. The current study was designed to examine this hypothesis. Methods/Procedures Fifty-eight participants with either DSM-IV-TR schizophrenia or schizoaffective disorder entered into a 6-week double-blind, placebo-controlled, double-dummy, randomized clinical trial of intranasal oxytocin and galantamine. Seventeen participants were randomized to intranasal oxytocin, 20 were randomized to galantamine and 21 were randomized to placebo. The Scale for the Assessment of Negative Symptoms total score was used to assess change in negative symptoms (the primary outcome measure for oxytocin). The MATRICS Consensus Cognitive Battery composite score was used to assess cognition (the primary outcome measure for galantamine). Findings/Results There were no significant group differences for negative symptoms (oxytocin versus placebo: F=0.19, df=2, 47.4, p=0.83; galantamine versus placebo: F=0.41, df=2, 52.5, p=0.67). There were no significant group differences for cognitive impairments (galantamine versus placebo: t= 0.71, df=40, p=0.48; oxytocin versus placebo: t= 0.50, df=40, p=0.62). There were also no significant group differences for the functional capacity or ancillary symptom measures. Implications/Conclusions The lack of an efficacy signal for either compound precluded our ability to test whether pharmacological treatment pathways for negative symptoms and cognitive impairments overlap or are independent. (clinicaltrials.gov trial number: NCT01012167)

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

“…Of the 12 studies, only 2 documented adherence [62, 89]. However, both studies used a weekly pill count and medication review to check for adherence, which is not a foolproof method [90], and only participants who received 75% or more of their assigned study medication were included in the analysis [62, 89].…”

“…However, both studies used a weekly pill count and medication review to check for adherence, which is not a foolproof method [90], and only participants who received 75% or more of their assigned study medication were included in the analysis [62, 89]. Efficacy signal detection may be enhanced in future RCTs if all of these issues are addressed.…”

“…Two-thirds of the studies with galantamine and memantine identified in this article had a duration ≥12 weeks. Among the 4 studies [59-62] with a duration < 12 weeks, only one was associated with an efficacy signal [59]. Among 118 RCTs on CIAS, a large majority had a duration ≤8 weeks [63].…”

“…Of 12 studies, only 2 [62, 72] used the MATRICS Consensus Cognitive Battery (MCCB [73]). It is unclear how cognitive rating scales used in the other studies would translate to changes in the MCCB.…”

“…Only one study in Table 1 conducted a measurement of functional capacity [62]. The FDA-NIMH-MATRICS guidelines recommend using UCSD Performance-Based Skills Assessment (UPSA)-2 [81].…”