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06. D-Cycloserine: Potential Indications and Administration in Children and Adolescents

Published on August 1, 2022 Expired on August 1, 2025

David R. Rosenberg, M.D.

Chair of the Department of Psychiatry & Behavioral Neuroscience - Wayne State University School of Medicine

Key Points

  • D-cycloserine has been observed to possess antianxiety properties.
  • D-cycloserine only shows an extinction effect when paired with behavioral training.
  • There is evidence that D-cycloserine may:

 -Enhance exposure therapy.
 -Accelerate the therapeutic effect of CBT in OCD.
 -Support maintenance of social skills gains in ASD.

  • Current evidence does not support the use of D-cycloserine in youth with PTSD.

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Slides and Transcript

Slide 1 of 25

Let’s turn to video 6, D-cycloserine: Potential indications and administration in children and adolescents.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 1 of 25

Slide 2 of 25

Here is another example of a compound, D-cycloserine, that generated a lot of excitement, had tremendous promise. Some of it may have been realized but some is still a work in progress as we’ll discuss. This was originally introduced as an antibiotic to treat tuberculosis. D-cycloserine has also been observed to possess antianxiety properties. It’s a partial NMDA agonist at the glycine modulatory site which facilitates the opening of calcium channels attached to NMDA receptors and appears to have a role in the neural activity underlying learned associations and extinction of fear.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Scheeringa, M. S., & Weems, C. F. (2014). Randomized placebo-controlled D-cycloserine with cognitive behavior therapy for pediatric posttraumatic stress. Journal of Child and Adolescent psychopharmacology, 24(2), 69–77.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 2 of 25
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Slide 3 of 25

However, D-cycloserine only shows an extinction effect when paired with behavioral training and not when given alone. This is very important that this particular compound, D-cycloserine, is not a standalone medication and doesn’t seem to be effective necessarily with other medications. It seems to have its most potency in concert with a behavioral intervention as we’ll describe in detail momentarily.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 3 of 25

Slide 4 of 25

Potential indications. The anxiety disorders are a natural area where D-cycloserine would be tried. And evidence from research both in animals and adults suggest that D-cycloserine may in fact augment the effects of behavioral therapy in children and adolescents with anxiety disorders.
References:
  • Plaisted, H., Waite, P., Gordon, K., & Creswell, C. (2021). Optimising exposure for children and adolescents with anxiety, OCD, and PTSD: A systematic review. Clinical Child and Family Psychology Review, 24(2), 348–369.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
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Slide 5 of 25

But findings from three large scale reviews and meta-analysis of 29 open-label trials and randomized controlled trials of D-cycloserine administration relative to placebo for cognitive and behavioral therapy augmentation for children and adolescents with anxiety and related disorders that were OCD, PTSD found only minimal benefit.
References:
  • Plaisted, H., Waite, P., Gordon, K., & Creswell, C. (2021). Optimising exposure for children and adolescents with anxiety, OCD, and PTSD: A systematic review. Clinical Child and Family Psychology Review, 24(2), 348–369.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 5 of 25

Slide 6 of 25

Notably, these reviews also identified a lack of consistency across studies related to methodologies and outcome measures as well as a failure to incorporate potential optimization strategies identified during studies in adults which limited the ability to make reliable conclusions or draw meaningful comparisons between studies. So, this is where looking at subgroups, differences in the methodology, the patient population can really make it hard to compare different studies.
References:
  • Plaisted, H., Waite, P., Gordon, K., & Creswell, C. (2021). Optimising exposure for children and adolescents with anxiety, OCD, and PTSD: A systematic review. Clinical Child and Family Psychology Review, 24(2), 348–369.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 6 of 25
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Slide 7 of 25

Despite these mixed results from current trials which have yielded small and inconsistent effects, there is some evidence that D-cycloserine may enhance exposure therapy in young people. Future research on D-cycloserine is needed though to clarify mechanisms and disentangle its effects across disorders and should include consistent study conceptualizations, methodologic approaches, and outcome measures to enable more meaningful comparisons.
References:
  • Plaisted, H., Waite, P., Gordon, K., & Creswell, C. (2021). Optimising exposure for children and adolescents with anxiety, OCD, and PTSD: A systematic review. Clinical Child and Family Psychology Review, 24(2), 348–369.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 7 of 25

Slide 8 of 25

Now, as a potential indication for obsessive-compulsive disorder, this had tremendous promise and is another example where there was incredible excitement about how D-cycloserine may become part of the armamentarium in treating OCD. Several studies have examined D-cycloserine augmentation of cognitive behavioral therapy in children and adults with OCD but again the results have been mixed.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Pittenger C. (2015). Glutamatergic agents for OCD and related disorders. Current Treatment Options in Psychiatry, 2(3), 271–283.
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Slide 9 of 25

Three randomized controlled trials in OCD youth found no significant effect of D-cycloserine on OCD severity. Although patients taking D-cycloserine did experience moderate symptom improvement compared to placebo on the Children’s Yale-Brown Obsessive-Compulsive Scale, the CGI-Severity, and ADIS CSR.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Pittenger C. (2015). Glutamatergic agents for OCD and related disorders. Current Treatment Options in Psychiatry, 2(3), 271–283.
  • Storch, E. A., Murphy, T. K., Goodman, W. K., Geffken, G. R., Lewin, A. B., Henin, A., Micco, J. A., Sprich, S., Wilhelm, S., Bengtson, M., & Geller, D. A. (2010). A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Biological Psychiatry, 68(11), 1073–1076.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 9 of 25

Slide 10 of 25

Additionally, one randomized controlled trial found greater sustained improvement in the Children’s Yale-Brown Obsessive-Compulsive Scale scores in the D-cycloserine group compared to the placebo at one month post treatment. There was one study that did observe a significantly faster rate of treatment progress at the midpoint of the study in patients receiving D-cycloserine. And we know that it takes the SSRIs often a while to be effective in obsessive-compulsive disorder so hastening or making more rapid the response to treatment is obviously beneficial in this condition.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Pittenger C. (2015). Glutamatergic agents for OCD and related disorders. Current Treatment Options in Psychiatry, 2(3), 271–283.
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Slide 11 of 25

So D-cycloserine may accelerate the therapeutic effect of cognitive behavioral therapy in OCD patients and the greatest treatment effect may be limited to unmedicated cases.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Pittenger C. (2015). Glutamatergic agents for OCD and related disorders. Current Treatment Options in Psychiatry, 2(3), 271–283.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 11 of 25

Slide 12 of 25

So obviously, very important that the response with this agent may not be as good if a patient is on traditional medicines used to treat OCD such as the SSRIs but in unmedicated patients this may be an attractive option to accelerate the treatment effect.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Pittenger C. (2015). Glutamatergic agents for OCD and related disorders. Current Treatment Options in Psychiatry, 2(3), 271–283.
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Slide 13 of 25

These studies do provide additional support of the potential for D-cycloserine for OCD but additional research is needed to further elucidate exactly which OCD patients might benefit the most from D-cycloserine augmentation.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Pittenger C. (2015). Glutamatergic agents for OCD and related disorders. Current Treatment Options in Psychiatry, 2(3), 271–283.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 13 of 25

Slide 14 of 25

Autism spectrum disorder. Early studies in this area were very compelling suggesting a possible benefit for D-cycloserine as a monotherapy in autism spectrum disorder with up to 40% of patients showing improvement on the Clinical Global Impression-Improvement scale and nearly 60% demonstrating improvement on the ABC-C.
References:
  • Wink, L. K., Minshawi, N. F., Shaffer, R. C., Plawecki, M. H., Posey, D. J., Horn, P. S., Adams, R., Pedapati, E. V., Schaefer, T. L., McDougle, C. J., Swiezy, N. B., & Erickson, C. A. (2017). D-cycloserine enhances durability of social skills training in autism spectrum disorder. Molecular Autism, 8, 2.
  • Minshawi, N. F., Wink, L. K., Shaffer, R., Plawecki, M. H., Posey, D. J., Liu, H., Hurwitz, S., McDougle, C. J., Swiezy, N. B., & Erickson, C. A. (2016). A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders. Molecular Autism, 7(1).
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Slide 15 of 25

A randomized controlled trial in high functioning youth with autism spectrum disorder examining the efficacy of D-cycloserine plus peer-mediated social skills group intervention found decreased social deficits although between group treatment effects were not significant.
References:
  • Minshawi, N. F., Wink, L. K., Shaffer, R., Plawecki, M. H., Posey, D. J., Liu, H., Hurwitz, S., McDougle, C. J., Swiezy, N. B., & Erickson, C. A. (2016). A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders. Molecular Autism, 7(1).
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 15 of 25

Slide 16 of 25

A follow-up randomized controlled trial in children with autism spectrum disorder receiving short-term social skills intervention also found participants receiving weekly adjunctive D-cycloserine experience significantly increased benefit that was sustained three months after treatment. Thus, D-cycloserine appears to support maintenance of social skills gains made during short-term group therapy compared to placebo.
References:
  • Wink, L. K., Minshawi, N. F., Shaffer, R. C., Plawecki, M. H., Posey, D. J., Horn, P. S., Adams, R., Pedapati, E. V., Schaefer, T. L., McDougle, C. J., Swiezy, N. B., & Erickson, C. A. (2017). D-Cycloserine enhances durability of social skills training in autism spectrum disorder. Molecular Autism, 8, 2.
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Slide 17 of 25

These results I think are particularly significant given that previous studies have noted a lack of treatment durability following social skills intervention in autism spectrum disorder. So this would be a huge advantage if this is replicated and in fact we do find that D-cycloserine augmentation leads to the durability, rather, of short-term group therapy gains. Although current research is limited, findings from current research support additional studies to examine the potential efficacy for adjunctive use of D-cycloserine in autism spectrum disorder.
References:
  • Wink, L. K., Minshawi, N. F., Shaffer, R. C., Plawecki, M. H., Posey, D. J., Horn, P. S., Adams, R., Pedapati, E. V., Schaefer, T. L., McDougle, C. J., Swiezy, N. B., & Erickson, C. A. (2017). D-Cycloserine enhances durability of social skills training in autism spectrum disorder. Molecular Autism, 8, 2.
  • Minshawi, N. F., Wink, L. K., Shaffer, R., Plawecki, M. H., Posey, D. J., Liu, H., Hurwitz, S., McDougle, C. J., Swiezy, N. B., & Erickson, C. A. (2016). A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders. Molecular Autism, 7(1).
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 17 of 25

Slide 18 of 25

Posttraumatic stress disorder. Although cognitive behavioral therapy has been associated with significant reductions in PTSD symptoms, results from a randomized controlled trial found little evidence supporting adjunctive D-cycloserine treatment in youth with posttraumatic stress disorder. Therefore, while D-cycloserine adjunctive treatment with CBT appears effective for some anxiety disorders, current evidence does not support its use in youth with PTSD.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • Scheeringa, M. S., & Weems, C. F. (2014). Randomized placebo-controlled D-cycloserine with cognitive behavior therapy for pediatric posttraumatic stress. Journal of Child and Adolescent psychopharmacology, 24(2), 69–77.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 18 of 25
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Slide 19 of 25

Dosage and administration in D-cycloserine. In children and adolescents, most studies employed weight-adjusted dosages between 25 and 50 mg that were administered 30 to 60 minutes before exposure therapy.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A Meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 19 of 25

Slide 20 of 25

The good news is that D-cycloserine appears to be very well tolerated in children and adolescents with few side effects.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
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Slide 21 of 25

The most commonly reported side effects are headache, irritability, and depression. A rare but potentially serious side effect such as psychosis and convulsions has also been reported.
References:
  • Rosenberg, D., & Gershon, S. (2012). Pharmacotherapy of child and adolescent psychiatric disorders. John Wiley & Sons.
  • McGuire, J. F., Wu, M. S., Piacentini, J., McCracken, J. T., & Storch, E. A. (2017). A meta-analysis of D-cycloserine in exposure-based treatment: Moderators of treatment effficacy, response, and diagnostic remission. The Journal of Clinical Psychiatry, 78(2), 196–206. 
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 21 of 25

Slide 22 of 25

The key take-home points here are that D-cycloserine has been observed to possess antianxiety properties. However, D-cycloserine only shows an extinction effect when paired with behavioral training.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 22 of 25
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Slide 23 of 25

Despite mixed results from current trials which have yielded small and inconsistent effects, there is some evidence that D-cycloserine may enhance exposure therapy, accelerate the therapeutic effect of CBT in OCD and support maintenance of social skills gains during group therapy in autism spectrum disorder.
D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 23 of 25

Slide 24 of 25

Additionally, while D-cycloserine treatment with behavioral therapy appears effective for some anxiety disorder, current evidence does not support the use of D-cycloserine in youth with posttraumatic stress disorder.
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D-Cycloserine: Potential Indications and Administration in Children and Adolescents Slide 25 of 25

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07. Potential Indications of Topiramate in Children and Adolescents

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After completing this activity, the learner will be able to:

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Original Release Date: August 1, 2022

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