Augmentation strategies in obsessive–compulsive disorder

Figures & data

Figure 1. Evidence-based treatment flowchart for obsessive–compulsive disorder.

^†Less than 25% reduction in the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) total score and Clinical Global Impression (CGI)-I of 4 suggests nonresponse to treatment

^‡35% reduction in the Y-BOCS score or CGI-I of 1 or 2 suggest full response to treatment.

^§Partial response defined as 25–35% reduction in Y-BOCS score despite adequate treatment duration with SSRI.

^¶Have not achieved remission of symptoms (<16 on Y-BOCS) despite adequate treatment with SSRI.

^#Haloperidol may be especially useful in patients with comorbid tic disorder.

^††Olanzapine and quetiapine augmentation are options before proceeding to clomipramine augmentation.

CBT: Cognitive-behavior therapy; OFC: Orbitofrontal cortex; rTMS: Repetitive transcranial magnetic stimulation; SMA: Supplementary motor area; SSRI: Selective serotonin reuptake inhibitor.

Table 1. Randomized placebo-controlled trials of antipsychotic augmentation in treatment nonresponders/partial responders to selective serotonin reuptake inhibitors in obsessive–compulsive disorder.

Study (year)	Antipsychotic dosage in mg mean (SD)	Patients (n)	Duration (weeks)	Duration of last SSRI trial	Mean Y-BOCS change-A (%)	Responders	Comments	Ref.
McDougle et al. (1994)	Haloperidol; 6.2 (3.0)	A = 17; P = 17	4	Fluvoxamine 8 weeks	26	A: 64.7% vs P: 0%^‡	Haloperidol > placebo	[27]
McDougle et al. (2000)	Risperidone; 2.2 ± 0.7	A = 20; P = 16	6	Any SSRI 12 weeks	31.8	A: 50% vs P: 0%^‡,§	Risperidone > placebo	[29]
Hollander et al. (2003)	Risperidone; 2.25 (0.86)	A = 10; P = 6	8	Any SSRI 12 weeks	19.04	A: 40% vs P: 0%^¶	Risperidone > placebo	[38]
Erzegovesi et al. (2005)	Risperidone; 0.5	A = 20; P = 19	6	Fluvoxamine 12 weeks^†	19.8	A: 50% vs P: 20%^‡	Risperidone significantly effective only in fluoxamine refractory patients	[39]
Bystrisky et al. (2004)	Olanzapine; 11.2 (6.5)	A = 13; P = 13	6	Any SSRI 12 weeks	16	A: 46% vs P: 0%^§	Olanzapine > placebo^#	[50]
Shapira et al. (2004)	Olanzapine; 6.1 (2.1)	A = 22; P = 22	6	Fluoxetine (20–40 mg) 8 weeks	12.75	A: 23% vs P: 18%^‡	Olanzapine = placebo	[30]
Atmaca et al. (2002)^††	Quetiapine; 91.1 (41.1)	A = 14;P = 13	8	Any SSRI 12 weeks	26.75	A: 64.4% vs P: 0%^‡	Quetiapine > placebo	[46]
Denys et al. (2004)	Quetiapine; 300	A = 20; P = 20	8	Any SSRI 8 weeks	31	A: 40% vs P: 20%^‡	Quetiapine > placebo	[43]
Carey et al. (2005)	Quetiapine; 168.75 (120.82)	A = 20; P = 21	6	Any SSRI 12 weeks	17.75	A: 40% vs P: 47.6%^§	Quetiapine = placebo	[31]
Fineberg et al. (2005)	Quetiapine; 215 (124)	A = 11; P = 10	16	Any SSRI 12 weeks	14	A: 27% vs P:10%^§	Quetiapine = placebo	[44]
Kordon et al. (2008)	Quetiapine; 400–600	A = 20; P = 20	12	Any SSRI 12 weeks	22	A: 65% vs P: 44%^‡	Quetiapine = placebo	[45]
Muscatello et al. (2011)	Aripiprazole; 15	A = 16; P = 14^¶	16	Any SSRI 8 weeks	28.5	A: 25%^‡	Aripiprazole > placebo	[54]
Sayyah et al. (2012)	Aripiprazole; 10	A = 18; P = 21	12	Any SSRI 12 weeks	29.5	A: 53% vs P: 17.6%^§	Aripiprazole > placebo	[21]

^†Responders to SSRIs included.

^‡Response criteria ≥35% decrease in Y-BOCS.

§Completer analysis showed no difference, high dropout.

¶Response criteria ≥25% decrease in Y-BOCS.

^#Only in SSRI nonresponders.

^††Single blind study.

SD: Standard deviation; SSRI: Selective serotonin reuptake inhibitor; Y-BOCS: Yale–Brown Obsessive Compulsive Scale.

Table 2. Randomized controlled trials of antipsychotic augmentation with active comparators.

Study (year)	Method	Drugs compared	N (completers)	Duration of trial	SSRI	Results	Ref.
Li et al. (2005)	Double-blind, placebo-controlled, crossover study	Risperdone (1 mg/day) vs haloperidol (2 mg/day) vs placebo	16 (12)	2 weeks of each drug	Any SSRI for 12 weeks	Active drugs > placebo	[40]
Maina et al. (2008)	Single-blind randomized trial	Olanzapine (2.5–10 mg) vs risperidone (1–3 mg)	50	8 weeks	Any SSRI 16 weeks	Both drugs equally effective	[51]
Diniz et al. (2010)	Double-blind, placebo-controlled trial	Clomipramine (≤75 mg) vs quetiapine (≤200 mg) vs placebo added to fluoxetine (40–80 mg)	54	12	Fluoxetine 8 weeks	Placebo + fluoxetine and clomipramine + fluoxetine > quetiapine + fluoxetine	[69]

Table 3. Randomized controlled trials on the augmentation efficacy of other interventions in obsessive–compulsive disorder.

Study (year)	Intervention arms	Duration	Study population	Results	Ref.
Soltani et al. (2010)	Ondansetron (4 mg) vs placebo + fluoxetine	8 weeks	42 drug-free OCD patients	Ondansetron > placebo	[63]
Aksari et al. (2012)	Granisetron (1 mg b.i.d.) vs placebo + fluoxamine	8 weeks	42 OCD patients with Y-BOCS >21	Granisetron (100% response) > placebo (35%)	[64]
Pallanti et al. (2004)	Mirtazapine (15–30 mg) vs placebo + citalopram^†	2 weeks	49 OCD patients	Earlier response to mirtazapine group, but no difference in final outcome	[66]
Grady et al. (1993)	Buspirone (60 mg/day) vs placebo + fluoxetine^‡	4 weeks each arm	14 OCD patients on stable dose of fluoxetine for 10 weeks	Buspirone = placebo	[70]
Crocket et al. (2004)	Clonazepam vs placebo + sertraline	12 weeks	37 OCD patients	Clonazepam = placebo	[71]
Dannon et al. (2000)	Pindolol (2.5 mg/day) vs placebo + paroxetine	6 weeks	14 patients resistant to 2 SSRIs	Pindolol > placebo	[74]
Mundo et al. (1998)	Pindolol vs placebo + fluoxamine	12 weeks	15 OCD patients	Pindolol = placebo	[75]
Ghaleiha et al. (2012)	Memantine (20 mg/day) vs placebo + fluoxamine	8 weeks	42 OCD patients	Memantine > placebo	[82]
Bruno et al. (2012)	Lamotrigine (100 mg/day) vs placebo + SSRI	16 weeks	33 treatment-resistant OCD patients	Lamotrigine > placebo	[83]
Mowla et al. (2011)	Topiramate (100–200 mg/day) vs placebo + SSRI	12 weeks	49 treatment-resistant OCD patients	Topiramate > placebo	[84]
Berlin et al. (2011)	Topiramate (50-400 mg/day) vs placebo + SSRI	12 weeks	36 OCD patients on SSRIs	Topiramate > placebo more adverse effects	[85]
Greenberg et al. (2009)	Glycine (60 mg/day) vs placebo + SSRI	12 weeks	14 OCD patients on stabilized treatment	Glycine nonsignificant improvement – poor tolerability	[90]
Koran et al. (2009)	D-amphetamine 30 mg/day vs caffeine 300 mg/day + SSRI/SNRI	5 weeks	24 OCD patients with adequate trial of SSRI/SNRI	Both effective; response rate; d-amphetamine: 50%; caffeine: 58%	[92]
Koran et al. (2005)	Weekly oral morphine vs lorazepam vs placebo + SSRI^‡	2 weeks each arm	23 OCD patients with at least 2 failed SSRI trials	Morphine > placebo	[96]
Tolin et al. (2007)	Self administered ERP vs therapist administered ERP^§	Therapist group: 7.5 weeks; self-group: 6 weeks	41 patients on adequate medication trial	Therapist administered ERP > self-administered ERP	[103]
Simpson et al. (2008)	ERP vs stress management training + SSRI	17 twice-weekly sessions	108 OCD patients on SSRI trial	ERP > stress management	[104]
Franklin et al. (2011)	Medication management alone vs medication management plus instruction in CBT vs medication management plus CBT	12 weeks	124 OCD patients (7–17 years) on SSRI trial	CBT was more effective	[105]
Mantovani et al. (2010)	Low frequency rTMS over SMA/sham rTMS + SSRI	4 weeks double blind	21 medication-resistant patients	Active rTMS group > sham rTMS	[107]

^†Single blinded.

^‡Double-blind crossover trial.

^§Open-label trial.

b.i.d.: Twice daily; CBT: Cognitive-behavior therapy; ERP: Exposure and response prevention; OCD: Obsessive–compulsive disorder; rTMS: Repetitive transcranial magnetic stimulation; SMA: Supplementary Motor Area; SSRI: Selective serotonin reuptake inhibitor; Y-BOCS: Yale–Brown Obsessive Compulsive Scale.

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