Is D-cycloserine effective and safe for social and communication skills deficits in people with ASD?

What is the aim of this review?

Autism spectrum disorder (ASD) is a relatively common disorder involving the abnormal development of the brain. It often leads to repetitive behaviours, restrictive activities, limited interests, reduced social functioning and language skills. There are no effective treatments for these features of ASD but recent research suggests that D-cycloserine might improve social and communication skills in people with ASD. D-cycloserine is a type of medicine used to treat tuberculosis (a contagious infection that usually affects the lungs) and schizophrenia (a serious mental disorder of thought, emotion and behaviour).  We wanted to know whether D-cycloserine, alone or in combination with other treatment, was better or worse than placebo (dummy pill) at improving social and communication skills in individuals with ASD. We also wanted to know if there were any harmful side effects from using this medication. 

Key messages

There appears to be no clear difference between D-cycloserine plus social skills training and social skills training alone on social and communication skills in individuals with ASD. However, we are uncertain about these results.

What was studied in the review?

We searched databases of scientific studies and found one relevant study to include in this review. The study took place in the USA and did not have industry funding. A total of 67 children aged 5 to 11 years were included in the study. One group took a medicine called D-cycloserine once a week plus social skills training, and the other group took a placebo pill (dummy pill which does not include medicine) plus social skills training. The treatment lasted for 10 weeks.

What are the main results of the review?

One week post-treatment, there was no difference in social interaction, repetitive behaviours and language skills between the D-cycloserine and placebo groups. Compared to placebo treatment, D-cycloserine may not increase the number of harmful side effects, the number of people dropping out of the study and treatment responsiveness.

D-cycloserine may make little or no difference to social and communication skills deficits in individuals with ASD. These findings may change if more studies are included. We do not know the long-term effects of D-cycloserine due to the short duration of the study.

How up-to-date is this review?

The review authors searched for studies that had been published up to November 2020.

Authors' conclusions: 

We are unable to conclude with certainty whether D-cycloserine is effective for individuals with ASD. This review included low certainty data from only one study with methodological issues and imprecision. The added value of this review compared to the included study is we assessed the risk of bias and evaluated the certainty of evidence using the GRADE approach. Moreover, if we find new trials in future updates of this review, we could potentially pool the data, which may either strengthen or decrease the evidence for our findings.

Read the full abstract...
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 strategy: 

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 between the two groups for all outcomes measured at one week post-treatment: social interaction impairment (mean difference (MD) 3.61 (assessed with the Social Responsiveness Scale), 95% confidence interval (CI) -5.60 to 12.82); social communication impairment (MD -1.08 (measured using the inappropriate speech subscale of the Aberrant Behavior Checklist (ABC)), 95% CI -2.34 to 0.18); restricted, repetitive, stereotyped patterns of behaviour (MD 0.12 (measured by the ABC stereotypy subscale), 95% CI -1.71 to 1.95); serious adverse events (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31); non-core symptoms of ASD (RR 0.97 (measured by the Clinical Global Impression-Improvement scale), 95% CI 0.49 to 1.93); and tolerability of D-cycloserine (RR 0.32 (assessed by the number of dropouts), 95% CI 0.01 to 7.68). 

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