D-Cycloserine Augmented Exposure Therapy for Obsessive-Compulsive Disorder

Kushner, Matt G.; Kim, Suck Won; Donahue, Christopher B.; Thuras, Paul; Adson, David E.; Kotlyar, Michael; McCabe, James S.; Peterson, Jillian K.; Foa, Edna B.

doi:10.1016/j.biopsych.2006.12.020

Cited by 363 publications

(265 citation statements)

References 12 publications

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“…It was hypothesized that d-cycloserine could enhance the effects of CBT. However, the results of DBPC studies in OCD were disappointing (Kushner et al 2007;Storch et al 2007;Wilhelm et al 2008)(E).…”

Section: )(E)mentioning

confidence: 99%

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

Bandelow

Zohar

Hollander

et al. 2008

The World Journal of Biological Psychiatry

718

410

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In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo-or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/ SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

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Section: )(E)mentioning

confidence: 99%

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

Bandelow

Zohar

Hollander

et al. 2008

The World Journal of Biological Psychiatry

718

410

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“…In recent years it has been demonstrated that d-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist, can enhance exposure therapy. This has been demonstrated pre-clinically in rats using the animal model of exposure therapy (extinction; Walker et al, 2002;Ledgerwood et al, 2003), and in human clinical trials with a range of anxiety disorders (Ressler et al, 2004;Hofmann et al, 2006;Kushner et al, 2007;Guastella et al, 2008).…”

Section: Introductionmentioning

confidence: 95%

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

Graham

Richardson

2009

Neuropsychopharmacol

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Despite having made substantial advances in the treatment of anxiety disorders over the past few decades it appears that we have now reached a 'therapeutic impasse'. Further clinical progress requires a greater understanding of the neural mechanisms underlying fear inhibition. In this study, we examined, for the first time, the effects of fibroblast growth factor-2 (FGF2), a mitogen involved in the molecular cascade of memory, on extinction and relapse in rats. In all experiments, rats were first trained to fear a white noiseconditioned stimulus, and then had this learned fear extinguished the following day. Extinction is the process underlying exposure-based therapy in humans. Experiments 1 and 2 demonstrated that FGF2 facilitated the loss of learned fear (ie, extinction) when given either prior to or immediately after extinction but not when given 4 h after extinction. This suggests that FGF2 must be present during the consolidation of the extinction memory to have an effect. Experiment 3 further supported this interpretation by showing that short-term extinction must occur for FGF2 to facilitate long-term extinction, suggesting that FGF2 is facilitating the translation of memory from short-term to long-term storage. In experiment 4 rats given FGF2 immediately after extinction exhibited less shock-induced reinstatement, which is a model preparation of relapse, than did vehicle-treated rats. Together, these experiments demonstrate that FGF2 facilitates extinction and attenuates relapse. Thus, FGF2 may be a novel pharmacological adjunct to exposure therapy.

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“…The most successful of these has been d-cycloserine (DCS), a partial N-methyl-Daspartate receptor agonist that has been shown to enhance extinction in rats (Walker et al, 2002;Ledgerwood et al, 2003) and exposure therapy in humans with social phobia (Hofmann et al, 2006;Guastella et al, 2008), obsessive compulsive disorder (Kushner et al, 2007), and acrophobia (Ressler et al, 2004). One attractive feature of DCS is that it has been shown to reduce reinstatement (Ledgerwood et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor-2 Enhances Extinction and Reduces Renewal of Conditioned Fear

Graham

Richardson

2010

Neuropsychopharmacol

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Anxiety disorders are increasingly prevalent in society; hence, there is a need to improve on existing treatments for such disorders. Fibroblast growth factor-2 (FGF2), a mitogen that is involved in brain development and regeneration, has been shown to both facilitate long-term extinction of fear and reduce stress-precipitated relapse in rats. Extinction is the laboratory analog of exposure-based therapies in humans. In this study, we continued to investigate the clinical potential of FGF2 as a pharmacological enhancer of extinction by examining its effect on renewal, a common type of relapse. In all experiments, rats were trained to fear a white noise-conditioned stimulus, and then this learned fear was extinguished the following day. Rats received systemic injections of FGF2 or vehicle immediately after extinction training. At test, on the day after extinction training, levels of freezing elicited by the white noise in either the extinction context or the original training context were measured. FGF2-treated rats showed less renewal of fear when tested in the original training context than did vehicle-treated rats. This pattern occurred even when vehicle rats were given double the amount of extinction training, and when FGF2-treated rats were given equivalent exposure to the extinction context. These results show that FGF2 facilitates long-term extinction and attenuates relapse, and thus highlight its potential as a novel pharmacological adjunct to exposure therapy.

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D-Cycloserine Augmented Exposure Therapy for Obsessive-Compulsive Disorder

Cited by 363 publications

References 12 publications

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

Fibroblast Growth Factor-2 Enhances Extinction and Reduces Renewal of Conditioned Fear

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