Treatment Resistant Obsessive-Compulsive Disorder

Treatment Resistant Obsessive-Compulsive Disorder (OCD) is defined as patients who have undergone an adequate trial of SRI (clomipramine or SSRI) and do not respond or show unsatisfactory results. This account for 40-50% of OCD patients. What other strategies can you employ in these patients?

 

(1) Add Pindolol: 2.5 mg TID

 

Mechanism: Beta-blocker and 5-HT1A presynaptic receptor antagonist –> increases serotonergic transmission through its effect on the presynaptic 5-HT1A receptor.

 

  • n= 14 treatmentresistant OCD patients were treated with paroxetine for 17+/-2 weeks up to 60 mg/d after they failed at least two other SSRI trials.
  • These patients who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebocontrolled Pindolol (2.5 mg three time daily) augmentation.

Results:

    1. Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS.

 

  1. Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted.

 

Source: Eur Neuropsychopharmacol. 2000 May;10(3):165-9.

 

(2) Add Haloperidol: 2-10 mg/daily

 

Study 1:

  • 62 patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine.
  • n= 34 of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n = 17) or placebo (n = 17) added to ongoing fluvoxamine treatment. 
  • Haloperidol dose: initiated at 2 mg and increased to a maximum of 10 mg/day.

 

Results:

  1. Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-compulsive symptoms as measured by the Y-BOCS.
  2. Eight of eight patients with comorbid chronic tic disorders, such as Tourette’s disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment.
  3. Note: Haloperidol addition was of little benefit in treating OCD patients without tics. 

 

Source: Arch Gen Psychiatry. 1994 Apr;51(4):302-8.

Study 2:

  • 9-week, double-blind, placebo-controlled, crossover study comparing the benefits of 2-week adjunctive treatments with risperidone, haloperidol, and placebo in patients with treatment resistant OCD 
  • n=16 patients were enrolled and 12 completed the study.
  • Dose: Haloperidol 2 mg/day; Risperidone 1 mg/day.

 

Results:

  1. For Obsessions: both risperidone and haloperidol significantly reduced obsession (p < .05) when compared with placebo.
  2. For Compulsions: There was a tendency that haloperidol, and to a lesser degree risperidone, also reduced the compulsion. (likely reason is lower doses of risperidone used).

 

Source: J Clin Psychiatry. 2005 Jun;66(6):736-43.

 

(3) Add Risperidone: 2 mg/daily

 

Study 1:

  • n=36 patients refractory to the SRI were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition
  • Dose: Risperidone was initiated at 1 mg/day, and the dose was increased by 1 mg weekly. The mean final risperidone dose was only 2.2 mg/day (SD=0.7 mg/day; range=1–4).

 

Results:

  1. 9 (50%) of 18 risperidone treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005).
  2. Seven (50%) of 14 patients who received open-label risperidone addition responded.
  3. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. 

 

Source: Arch Gen Psychiatry. 2000 Aug;57(8):794-801.

Study 2:

  • double-blind, placebo-controlled trial
  • n= 16 adult treatmentresistant OCD patients were randomly assigned to augmentation with 8 wk of either risperidone (n=10) (0.5-3.0 mg/d) or placebo (n=6) following at least 12 wk of SRI treatment.
  • Dose: Risperidone was started at 0.5 mg/day, and the dose was increased by 0.5 mg weekly to a maximum of 3 mg/day; the mean risperidone dose was 2.25 mg/day.

 

Results:

  1. Four patients on risperidone (40%) and none (0%) on placebo were responders.
  2. Risperidone was generally well tolerated.
  3. Better Y-BOCS insight score at baseline significantly correlated with a greater CGI-I score at endpoint on risperidone augmentation

 

Source: Int J Neuropsychopharmacol. 2003 Dec;6(4):397-401.

Study 3:

  • n= 39 obsessive-compulsive inpatients completed the study.
  • All patients received 12 weeks of a standardized open-label fluvoxamine monotherapy and then continued for 6 weeks with placebo or risperidone in a double-blind design.
  • Dose: risperidone 0.5 mg/day.

 

Results:

  1. Significant effect of risperidone addition seen at the end of the double-blind phase (18th week) but only for fluvoxamine-refractory patients.
  2. Five patients on risperidone (50%) and two (20%) on placebo became responders.
  3. This preliminary study suggests that even very low (0.5 mg) risperidone doses are effective in OC patients who were nonresponders to a standardized treatment with fluvoxamine.

 

Source: Eur Neuropsychopharmacol. 2005 Jan;15(1):69-74.

 

(4) Add Olanzapine (date not consistent): 

 

Study 1:

  • n=26 with treatment resistance OCD were treated for 6 weeks in a double-blind, placebo-controlled augmentation study with either olanzapine (up to 20 mg/day) or placebo.
  • Mean olanzapine dose was 11.2 mg/day (SD=6.5; range: 5–20 mg/day)

 

Results:

  1. Six (46%) of 13 subjects in the olanzapine group showed a 25% or greater improvement in Y-BOCS score compared with none in the placebo group. 

 

Source: J Clin Psychiatry. 2004 Apr;65(4):565-8

Study 2:

  • 6-week, placebocontrolled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject).

 

Results:

  1. Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] a
  2. However, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine.
  3. These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial.

 

Source: Biol Psychiatry. 2004 Mar 1;55(5):553-5.

 

(5) Inositol (will benefit minority of OCD patients) 

 

Inositol is a precursor in the phosphatidylinositol cycle. Inositol is reported to reverse desensitization of serotonin receptors hence is hypothesized to benefit OCD symptoms. 

Study 1:

  • n= 13 patients with OCD completed a double-blind controlled crossover trial of 18 gm inositol or placebo for six weeks each.

 

Results:

  1. Inositol significantly reduced scores of OCD symptoms compared with placebo.

 

Source: Eur Neuropsychopharmacol. 1997 May;7(2):147-55.

Study 2:

  • n= 10 treatment resistant OCD patients participated in open-label trial of inositol (18 gm/day) augmentation for 6 weeks.

 

Results:

  1. The majority of patients (n = 7) did not respond to treatment with inositol augmentation on the CGI improvement item.
  2. Mean Y-BOCS scores fell significantly from 23.6 (±4.4) to 17.6 (±4.6).
  3. However, a small number of patients (n = 3) did report a clinically significant response on the CGI improvement item.
  4. Unfortunately, inositol augmentation of a SRI did not lead to significant improvement in the majority of such cases.

 

Source: Int Clin Psychopharmacol. 1999 Nov;14(6):353-6.

 

(6) Morphine Sulphate (30-45 mg once weekly)

 

Mechanism of Action is unknown.

Study 1:

  • n= 23 patients with treatment resistant OCD were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. Week 2 dosage was increased, decreased, or maintained depending on response and side effects.
  • Dose: 30-45 mg weekly

 

Results:

  1. The median Y-BOCS score after morphine (highest dose) was 25 (median decrease = 13%): 7 subjects (30%) were responders.
  2. The median Y-BOCS score after lorazepam (highest dose) was 27 (median decrease = 6%): 4 subjects (17%) responded to lorazepam;
  3. The median Y-BOCS score after placebo (highest dose) was 27 (median decrease = 7%), and no subject responded.
  4. This results support the hypothesis that once-weekly oral morphine can reduce symptoms in some treatment-resistant OCD patients.

 

Source: J Clin Psychiatry. 2005 Mar;66(3):353-9.

 

(7) Buspirone (60 mg daily- not as augmentation agent)

 

Study 1:

  • n= 18 outpatients with obsessive-compulsive disorder were treated with either buspirone 60mg daily or clomipramine 250 mg daily in a double-blind, random-assignment study.

 

Results:

  1. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales.
  2. This preliminary result warrants further exploration with a larger sample and other serotonergic agents.

 

Source: Am J Psychiatry. 1991 Jan;148(1):127-9.

Note: other studies did not showed improvement in YBOCS with Buspirone augmentation. 

Source: 

  1. J Clin Psychopharmacol 1992; 12:11–18
  2. Am J Psychiatry 1993; 150:647–649

Source: APA Practice Guidelines.


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Dr. Harvinder Singh, M.D. (Admin)


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