Pharmacogenetics of Obsessive-Compulsive Disorder: An Evidence-Update

Resolution of Selective Serotonin Reuptake Inhibitor–Associated Sexual Dysfunction After Switching From Fluvoxamine to Fluoxetine

“…In the last case, EPS adverse effects occurred at a dose of 25 mg/d and on the 10th day of treatment. [5][6][7]10 In our case, unlike those reported in these 3 case reports, acute dystonia occurred at a dose of 25 mg/d and on the third day of treatment.…”

“…This is seen in our case wherein the patient's symptoms were not resolved with high doses of 1 SSRI that has successfully treated OCD in many patients, but his symptoms were resolved with another SSRI. Pharmacogenetics is especially important in psychiatry because at present almost 50% of people who take psychotropic medications do not respond to them as expected, which may be due to metabolic pathway and receptor variation 4,5 …”

“…In addition to the minor mechanistic differences between the SSRIs, there are individual differences in patient factors such as metabolism, receptor subtypes, and enzymatic activity that can contribute to the differential responsiveness and experiences of adverse effects. 4,5 Furthermore, not only does the impact of SSRIs vary between medications in the class at both the behavioral and molecular levels, but also these effects differ depending on length of medication administration.…”

“…Although the main mechanism of the SSRI drug class is serotonin reuptake inhibition, there are variations within the drug class based on selectivity for serotonin versus noradrenaline, elimination half-life, receptor affinity, and impact on metabolism (eg, CYP inhibition) 1,3 ; these minor mechanistic differences across SSRIs contribute to our understanding of the differential responsiveness to medications within the same drug class. In addition to the minor mechanistic differences between the SSRIs, there are individual differences in patient factors such as metabolism, receptor subtypes, and enzymatic activity that can contribute to the differential responsiveness and experiences of adverse effects 4,5 . Furthermore, not only does the impact of SSRIs vary between medications in the class at both the behavioral and molecular levels, but also these effects differ depending on length of medication administration.…”

Potential therapeutic mechanism of deep brain stimulation of the nucleus accumbens in obsessive-compulsive disorder

“…To be specific, the dopaminergic projections to the NAc mainly originate from the VTA ( Figure 1A ) ( Hadley et al, 2014 ; Lammel et al, 2014 ; Cooper et al, 2017 ), the serotonergic projections to the NAc mainly originate from the raphe nuclei (RN) ( Figure 1C ) ( Modell et al, 1989 ; Kiyasova et al, 2011 ; Alonso et al, 2013 ; Kim et al, 2019 ), histaminergic projections to the NAc mainly originate from the tuberomammillary nucleus (TMN) ( Figure 1E ) ( Zhang et al, 2020 ; Manz et al, 2021 ), cholinergic projections to the NAc mainly originate from the basal forebrain (BF) and pontomesencephalo-tegmental complex (PTC) ( Figure 1G ) ( Mark et al, 2011 ; Laurent et al, 2014 ; Luchicchi et al, 2014 ; Gielow and Zaborszky, 2017 ), and glutamatergic projections to the NAc mainly originate from the broad cortex, hippocampus (CA) and basolateral amygdala (BLA) ( Figure 1I ) ( Walaas, 1981 ; Tarazi et al, 1998 ; Saul’skaya and Mikhailova, 2003 ; Zhu et al, 2022 ). Recently, some studies have revealed changes in the levels of these neurotransmitters and relevant receptors in OCD, and it is believed that the disturbances of these substances especially in the regions related to the cortico-striato-thalamico-cortical (CSTC) circuitry are normally considered as the basis of OCD ( Winslow and Insel, 1990 ; Fineberg et al, 2011 ; van Dijk et al, 2012 ; Haleem et al, 2014 ; Pittenger, 2015 ; Ade et al, 2016 ; Vlček et al, 2018 ; Zhan et al, 2020 ; Zai, 2021 ). Nevertheless, research on the neurotransmitters that play a role in the NAc is lacking, and it is still not clear how the activity of these substances changes in OCD patients after NAc-DBS.…”