While the meta-study only reviewed studies about blocking the 5-HT3 receptor, other studies listed below directly implicate the 5-HT1, 5-HT2 and 5-HT7 receptors as well, which strengthens the hypothesis that serotonin (5-HT) as a whole is the driver of OCD. In addition, consider the fact that the drug Meta-Chlorophenylpiperazine (mCPP) is perhaps the most widely-used and well-researched agent for causing/exacerbating OCD. That drug is also the perfect synthetic surrogate of serotonin - i.e. it is an agonist on most 5-HT receptors, it increases serotonin release, and also acts as an SSRI. Hard to get more serotonergic than this.
https://en.wikipedia.org/wiki/Meta-Chlorophenylpiperazine
The old ergot derivative metergoline - a non-selective serotonin antagonist - has been shown to block the pro-OCD effects of mCPP.
https://pubmed.ncbi.nlm.nih.gov/2018816/
To me at least, the evidence above alone means cased closed on the causes and cures of OCD, but since it is only one study I decided to also add the ones below. If that hypothesis is correct, then the current treatment of OCD with the serotonergic SSRI drugs is nothing short of criminally negligent and may explain to a great degree why OCD rates continue rising (especially in children and young adults) - i.e. the rising usage of SSRI drugs by those age groups are likely directly contributing to the rising rates of OCD.
Patients with obsessive–compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei
Essential role for orbitofrontal 5-HT1B receptors in OCD-like behavior and SRI response in mice
APA PsycNet
The 5-HT7 receptor influences stereotypic behavior in a model of obsessive-compulsive disorder - PubMed
www.physiciansweekly.com
"...Pooled 5-HT3R-As outperformed placebo regarding Y-BOCS total score (MD = -5.08, 95% CI = -7.04, -3.12, N = 9, n = 560), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, and remission rate. Individually, all 5-HT3R-As outperformed placebo regarding Y-BOCS total score (granisetron: MD = -5.59, 95% CI = -8.79, -2.39, N = 3, n = 178, ondansetron: MD = -5.72, 95% CI = -8.06, -3.37, N = 6, n = 331, tropisetron: MD = -2.87, 95% CI = -5.19, -0.550, N = 1, n = 96). However, all-cause discontinuation and incidence of individual adverse events between pooled 5-HT3R-As and placebo were not significantly different. In conclusion, our meta-analysis suggested 5-HT3R-As as efficacious for symptom improvement in individuals with OCD. However, the number of individuals included in each study was small; thus, a replication randomized trial of 5-HT3R-As should be conducted using a larger sample size."
https://en.wikipedia.org/wiki/Meta-Chlorophenylpiperazine
The old ergot derivative metergoline - a non-selective serotonin antagonist - has been shown to block the pro-OCD effects of mCPP.
https://pubmed.ncbi.nlm.nih.gov/2018816/
To me at least, the evidence above alone means cased closed on the causes and cures of OCD, but since it is only one study I decided to also add the ones below. If that hypothesis is correct, then the current treatment of OCD with the serotonergic SSRI drugs is nothing short of criminally negligent and may explain to a great degree why OCD rates continue rising (especially in children and young adults) - i.e. the rising usage of SSRI drugs by those age groups are likely directly contributing to the rising rates of OCD.
Patients with obsessive–compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei
Essential role for orbitofrontal 5-HT1B receptors in OCD-like behavior and SRI response in mice
APA PsycNet
The 5-HT7 receptor influences stereotypic behavior in a model of obsessive-compulsive disorder - PubMed
Serotonin 3 receptor antagonists for obsessive-compulsive disorder: A systematic review and pairwise meta-analysis. - Physician's Weekly
The benefits of serotonin 3 receptor antagonists (5-HT3R-As) in obsessive-compulsive disorder (OCD) treatment remain unclear. Thus, this study aimed to perform a systematic review and a random-effects meta-analysis, including double-blind, randomized, placebo-controlled trials (DBRPCTs). The...
www.physiciansweekly.com
"...Pooled 5-HT3R-As outperformed placebo regarding Y-BOCS total score (MD = -5.08, 95% CI = -7.04, -3.12, N = 9, n = 560), Y-BOCS obsession subscale score, Y-BOCS compulsive subscale score, treatment response, and remission rate. Individually, all 5-HT3R-As outperformed placebo regarding Y-BOCS total score (granisetron: MD = -5.59, 95% CI = -8.79, -2.39, N = 3, n = 178, ondansetron: MD = -5.72, 95% CI = -8.06, -3.37, N = 6, n = 331, tropisetron: MD = -2.87, 95% CI = -5.19, -0.550, N = 1, n = 96). However, all-cause discontinuation and incidence of individual adverse events between pooled 5-HT3R-As and placebo were not significantly different. In conclusion, our meta-analysis suggested 5-HT3R-As as efficacious for symptom improvement in individuals with OCD. However, the number of individuals included in each study was small; thus, a replication randomized trial of 5-HT3R-As should be conducted using a larger sample size."
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