Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan

We have conducted a pharmacological challenge experiment in 10 medication-free obsessive compulsive (OC) disorder (OCD) patients. We used a placebo-controlled paradigm for m-chlorophenylpiperazine (mCPP) and sumatriptan challenges. Endocrine, physiological and behavioral variables were assessed at baseline and over a 3-hour period after the challenge. Both cortisol and prolactin were significantly elevated in OCD patients following mCPP administration. Both mCPP and sumatriptan caused significant OC symptom exacerbation with the response to sumatriptan being more robust. We conclude that the 5-HT_1Dβ receptor may play a role in the pathophysiology of OCD.

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“…Thus, sumatripan [25] anism underlying this effectiveness might be related to adaptive downregulation.…”

Section: Discussionmentioning

confidence: 99%

Serotonergic Dissection of Obsessive Compulsive Symptoms: A Challenge Study with m-Chlorophenylpiperazine and Sumatriptan

et al. 2004

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“…Recently, Gross-Isseroff et al [4] reported that sumatriptan, a 5-HT1D ␤ agonist, caused significant exacerbations of OC symptoms. In addition, Stern et al [5] found that the chronic administration of sumatriptan could reduce depression and OC symptoms in 3 refractory OCD patients. For these reasons, the 5-HT1D ␤ receptor gene can be considered as a candidate gene for OCD.…”

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confidence: 99%

Association of a 5-HT1Dβ Receptor Gene Polymorphism with Obsessive-Compulsive Disorder in Korean Male Subjects

Kim

Namkoong²,

Kang³

et al. 2009

Neuropsychobiology

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The 5-HT1Dβ receptor gene appears to be particularly interesting in the pathophysiology of obsessive-compulsive disorder (OCD). The 5-HT1Dβ receptor is a terminal autoreceptor involved in the regulation of serotonin synthesis and release. We performed an association study of the G861C single nucleotide polymorphism (SNP) of the 5-HT1Dβ receptor in 167 male Korean OCD subjects and in 107 controls. Individuals with the G allele had an increased chance of having OCD (OR 1.49, 95% CI 1.05–2.10). Our findings suggest an association between the G861C SNP of the 5-HT1Dβ receptor and males with OCD. In the future, other tag SNPs that cover the entire 5-HT1Dβ gene region as well as additional SNPs that are supposed to have meaningful functions should be investigated in both male and female OCD subjects.

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“…4,6,7 On the other hand, the chronic administration of sumatriptan was found to improve symptoms in some OCD patients resistant to conventional pharmacotherapy. 8 We recently reported on significant linkage disequilibrium between the G861 allele of the 5HT1D␤ gene and OCD. 9 The specificity of this association has been supported by a more recent study reporting no association between the same marker and bipolar disorder.…”

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confidence: 99%

5HT1Dβ Receptor gene implicated in the pathogenesis of Obsessive-Compulsive Disorder: further evidence from a family-based association study

et al. 2002

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Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong evidence for a genetic component and for the involvement of genes of the serotonin system. In a recent family-based association study we reported an association between the G allele of the G861C polymorphism of the 5HT1D␤ receptor gene and OCD. The aim of the present study was to further investigate for the presence of linkage disequilibrium between each of two polymorphisms of the 5HT1D␤ receptor gene and OCD in a larger sample of OCD families. In a total of 121 families the G861C and the T371G polymorphisms of the 5HT1D␤ receptor gene were genotyped using standard protocols. The genotyping data were analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The phenotypes considered in the analyses were the diagnosis of OCD and two quantitative phenotypes related to the diagnosis and clinically relevant, ie, the age at onset and the severity of OCD symptoms. We confirmed the previously found preferential transmission of the G861 allele to the affected subjects (z = Obsessive-Compulsive Disorder (OCD) is a severe psychiatric condition affecting up to 3% of the general population lifetime. 1 The etiology of OCD remains obscure. However, there is strong evidence for a genetic component, 2 and for the involvement of the serotonin (5HT) neurotransmission. [3][4][5] The 5-HT1D␤ receptor is a terminal auto-receptor involved in the regulation of 5HT release. The acute administration of non-selective (ie, mCPP) or selective (ie, sumatriptan) ligands of the 5HT1D␤ receptor induces a transient worsening of OCD symptoms. 4,6,7 On the other hand, the chronic administration of sumatriptan was found to improve symptoms in some OCD patients resistant to conventional pharmacotherapy. 8 We recently reported on significant linkage disequilibrium between the G861 allele of the 5HT1D␤ gene and OCD. 9 The specificity of this association has been supported by a more recent study reporting no association between the same marker and bipolar disorder. 102

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Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan

Cited by 60 publications

References 20 publications

Serotonergic Dissection of Obsessive Compulsive Symptoms: A Challenge Study with m-Chlorophenylpiperazine and Sumatriptan

Serotonergic Dissection of Obsessive Compulsive Symptoms: A Challenge Study with m-Chlorophenylpiperazine and Sumatriptan

Association of a 5-HT1Dβ Receptor Gene Polymorphism with Obsessive-Compulsive Disorder in Korean Male Subjects

5HT1Dβ Receptor gene implicated in the pathogenesis of Obsessive-Compulsive Disorder: further evidence from a family-based association study

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