The effectiveness and adverse effects of D‐cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder

Background Symptoms of autism spectrum disorder (ASD) have been associated, in part, with the dysfunction of N‐methyl‐D‐aspartate (NMDA) glutamate receptors at excitatory synapses and glutamate abnormalities. Medications related to glutamatergic neurotransmission, such as D‐cycloserine ‐ which is a partial agonist of the NMDA glutamate receptor ‐ are potential treatment options for the core features of ASD. However, the potential effect of D‐cycloserine on the social and communication skills deficits of individuals with ASD has not been thoroughly explored and no systematic reviews of the evidence have been conducted. Objectives To assess the efficacy and adverse effects of D‐cycloserine compared with placebo for social and communication skills in individuals with ASD. Search methods In November 2020, we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers. We also searched the reference lists of relevant publications and contacted the authors of the included study, Minshawi 2016, to identify any additional studies. In addition, we contacted pharmaceutical companies, searched manufacturers' websites and sources of reports of adverse events. Selection criteria All randomised controlled trials (RCTs) of any duration and dose of D‐cycloserine, with or without adjunct treatment, compared to placebo in individuals with ASD. Data collection and analysis Two review authors independently selected studies for inclusion, extracted relevant data, assessed the risk of bias, graded the certainty of the evidence using the GRADE approach, and analysed and evaluated the data. We provide a narrative report of the findings as only one study is included in this review. Main results We included a single RCT (Minshawi 2016) funded by the United States Department of Defense. It was conducted at two sites in the USA: Indiana University School of Medicine and Cincinnati Children's Hospital Medical Centre. In the included study, 67 children with ASD aged between 5 and 11 years were randomised to receive either 10 weeks (10 doses) of (50 mg) D‐cycloserine plus social skills training, or placebo plus social skills training. Randomisation was carried out 1:1 between D‐cycloserine and placebo arms, and outcome measures were recorded at one‐week post‐treatment. The 'risk of bias' assessment for the included study was low for five domains and unclear for two domains. The study (67 participants) reported low certainty evidence of little to no difference betwee