Neuroendocrine predictors of response to intravenous clomipramine therapy for refractory obsessive-compulsive disorder

Abstract

The current study examines the neuroendocrine response to intravenous clomipramine (IV CMI) in oral CMI-resistant obsessive-compulsive disorder (OCD) patients on day 1 and day 14 of treatment to identify predictors of response. Forty-four OCD patients with an inadequate response or poorly tolerant to oral CMI were begun at 25 mg IV CMI, increasing to 250 mg by day 10, and continuing on that dose to day 14. On day 1, plasma levels of prolactin (PRL), growth hormone (GH), and cortisol were obtained immediately before the 25 mg IV infusion, and at five 30-minute time points after the infusion. On day 14, hormonal samples were obtained in a similar fashion. Response was assessed by the Clinical Global Impressions (CGI). Low PRL(MAX) to IV CMI and low cortisol levels overall on day 1 were both significantly associated with clinical response at day 14. An overall increase in growth hormone (GH) secretion during the day 14 testing was associated with positive response. A pronounced PRL response to IV CMI on day 14 was exhibited by the nonresponders, whereas a smaller and later but significant increase in PRL was noted in the responders. The findings suggest that in this sample of oral CMI-resistant patients with OCD, neuroendocrine measures derived from pharmacological challenge with IV CMI are capable of distinguishing IV CMI treatment responders from nonresponders. The limitations of IV CMI as a specific probe of serotonin function are discussed.

Diurnal Cortisol Levels and Cortisol Response in Youths with Obsessive-Compulsive Disorder

“…Previous studies in adults have been inconsistent, with some positive [33,62] and some negative results [22,32] . Likewise, we did not find any evidence of cortisol being predictive of the clinical course, as has been indicated previously [26] . Disparities and negative results may be due to power issues or the ceiling effects of the singlegroup correlation analyses.…”

“…Some results indicate a serotonin hyporesponsivity of the HPA axis in OCD patients resistant to therapy -which would indicate a defective link between these 2 systems -as an integral OCD trait marker [22][23][24] , although not all results support this [25] . The idea of a neuroendocrine trait marker is supported by results showing a predictive effect of cortisol reactions in clinical responses to intravenous pharmacological treatment in patients with refractory OCD [26] . Neuroanatomically, the anterior cingulate gyrus is proposed to be involved in the pathophysiology of OCD [20,27] and regulation of the HPA axis [28] .…”

Baseline and acute changes in the HPA system in patients with anxiety disorders: the current state of research

“…This finding might be explained by a more pronounced comorbid depressive symptomatology in PD patients reflected by mean HADRS score of 18 (vs a mean HADRS score of 4 in patients with OCD). For details of these studies, see In a sample of 44 oral clomipramine-resistant patients, Mathew et al conducted a challenge with clomipramine, which was administered intravenously over 14 days, and found that lower cortisol levels on day 1 were predictive of treatment response on day 14 [57].…”

“…In SAD, SP and PTSD, fenfluramine or a disorderspecific nonpharmacological challenge led to a higher cortisol response compared with healthy control subjects. Moreover, results in GAD or OCD suggested that therapeutic interventions are followed by changes in cortisol levels and baseline cortisol levels might have the potential to predict treatment response [40,41,57]. Again, these findings are only based on a maximum of two studies and need replication by further investigations.…”

Obsessive-Compulsive Disorder Spectrum as a Scientific “Metaphor”

“…Other investigators have argued for subtyping OCD according to the presence or absence of tics, since patients with comorbid tics show different symptoms, have earlier onset, tend to be male, and are less responsive to SRIs than those without tics. [27][28][29] Based on this view, this cluster of OCRD would be neurologically based and may involve Sydenham's chorea and autism, both of which also display repetitive behaviors. In these disorders, compulsions are repetitive motor behaviors that are stereotypical and are usually not accompanied by obsessions.…”