Treatment of Obsessive Compulsive Disorder

Dr. T.S. Jaisoorya

Consultant Psychiatrist

General Hospital

Ernakulam
Obsessive Compulsive disorder (OCD) is an intriguing and often debilitating syndrome characterized by the presence of obsessions and compulsions. Till the mid 1980s, OCD was considered extremely rare. This perception changed with results of the National Epidemiological Catchment Area (ECA) study and Cross National Collaborative Group Study which found OCD to be the fourth most common psychiatric disorder with a prevalence rate ranging from 0.8% to 2.3%.
The last decade has seen an expansion in appreciation of clinical features, co morbid patterns, genetic factors, role of specific neurotransmitters and brain circuitry in OCD. This relatively rapid paradigm shift has resulted in the introduction of new treatment methods-specific medications, therapies and new invasive techniques. These numerous treatment options that have recently emerged for obsessive compulsive disorder, necessitates a relook of the current practice parameters.
General Consideration
OCD should be viewed as a chronic illness with a waxing and waning course. Symptoms are often worse during times of psychosocial stress. Few patients experience a cure or complete remission of symptoms.
Most patients with OCD can be helped with modern pharmacological and behaviour therapies.
The goal of treatment are to reduce the frequency and intensity of symptoms as much as possible and to minimize the amount of interference the symptoms cause to a patients life.
Assessment
The first step in management is assessment. The Y-BOCS, a 10 items clinician administered scale, has become the most widely used rating scale for OCD. The clinicians should first ask the patient to complete the Y_BOCS symptoms checklist, and should review the completed checklist with the patient. This can be a first step in helping patients recognize all the thoughts and behaviour that are part of their illness, and allow the clinician and patient to agree on the symptoms being rated. The checklist can also be used to select target symptoms for treatment. The Y-BOCS rating scale provides five dimensions (one additional dimension in the 199 version - obsession/compulsion free interval - not to be scored) for obsessions and compulsions: time spent or occupied; interference with functioning or relationships; degree of distress; resistance; control; each scored on a four points scale from 0=no symptoms to 4=extreme symptoms. The sum of the first five items is a severity index for obsessions, and the sum of the last five an index for compulsions. A translation of total score into an approximate index of overall severity is: 0-7 Sub clinical, 8-15 mild, 16-23 Moderate, 24-31 severe, 32-40 extreme. A score of 16 or more indicates necessity to initiate treatment. A decrease of =35% is widely accepted as indicating a clinically meaningful response and translates into a global improvement rating of much or very much improved.
A comprehensive treatment plan will also include assessment of co morbidity. Depression and anxiety disorders are common co morbidities. The presence of a tic disorder, schizotypical or borderline personality disorder, ar a personal or family history of hypo mania or mania should be explored, since these would influence therapy choices.
With the exception of tic disorder, co morbid Axis I disorder do not seem to affect drug treatment adversely, although most large trails to date have excluded patients with co-morbid conditions of marked severity. Neither the presence of depression nor its severity (within the mild to moderate range) in for inhibitors. A poorer response to clomipramine or fluoxetine has been reported for patients with co morbid paranoid, schizoid or schizotypal personality disorder. The presence of borderline personality disorder interferes with treatment compliance.
Pharmacotherapy
The efficacy of clomipramine and of five SSRIs (Citalopram, Fluoxetine, Fluvoxamine, Paroxetine and Sertraline) has been established in multicenter, double-blind, placebo controlled trails. Together these studies suggest that:
. 40-60% of patients treated with a SRI will be improved or much improved.
. Treatment naive patients are more likely to respond to a SRI trail than patients who have failed a prior SRI trail
. Patients who do not respond to one SRI often respond to another
. In treating OCD, the effective dose of SRIs are often higher than those used to treat depressive disorders.
. Most patients do not experience substantial benefit before the sixth week of treatment.
. Patients who do not respond to lower SRI doses often respond to higher ones.
. An adequate SRI trail requires 10-12 weeks, Including at least six weeks at the maximum tolerated dose.
. The SSRIs are better tolerated than clomipramine
Table 1. Daily Dose for Primary anti-OCD drugs
(Recommendation by the Expert Consensus Guidelines for Treatment of OCD (March et al)
Medication Starting Dose Average target Maximum
Citalopram 20 40-60 60
Clomipramine 25-50 100-250 250
Fluvoxetine 20 40-60 80
Fluvoxamine 50 200 300
Paroxetine 20 50 60
Sertraline 50 150 225
The majority of controlled treatment trails have been performed with adult patients between ages of 18 and 65 years; however these therapies have been shown effective for patients of all ages. In general, children and the elderly tolerate most of these medications well. for children, Lower doses are indicated because of lower body mass. Use of lower doses should also be considered in the elderly because of their degreased ability to metabolize medication.
Two meta-analysis of clomipramine versus SSRI treatment of OCD have suggested that clomipramine has a greater therapeutic effect although the analyses included no parallel- group comparison studies (Griest et al., Piccinelli et al. ) None of the randomized, double-blind, parallel-group studies described subsequently has found clomipramine superior to an SSRI. But majority of the parallel-group comparison studies has found the SSRIs to be better tolerated than clomipramine. Patients who fail to respond to one or more SRI trails may be less likely than treatment naive patients to respond to the next SRI trial. Only about 30% who have had trial of SSRI respond in comparison to about 53% in treatment naive patients. There are no clinically useful predictors of which SRI will be effective for a given patient.
Other successful alternative monotherapies
Venlafaxine
Most data on venlafaxine is from open trials and case reports. In an eight week, double blind, placebo controlled trial of venlafaxine triturated up to 225 mg/day, neither the venlafaxine group nor the placebo group showed a statistically significant mean decrease in Y-BOCS. Case reports describe responses to 150mg/day, 225mg/day, 375mg/day. Taken together, these results suggest that if a venlafaxine trial is undertaken, the target dose should be at least 225mg/day. Clonazepam Will be discussed below
MAOI
Monamine oxidase inhibitors have been reported to relive OCD symptoms in a few cases characterized by co morbid panic disorder. Administration of MAOIs for OCD can follow the same dosage guidelines has for major depression. A double blind trial of phenelzine in OCD had showed a 35% responds with most patients who responded having symmetry obsessions. But there are numerous studies with disappointing findings. A phenelzine trial may be considered for a patients with symmetry obsessions who have failed several SRI trials. Sufficient wash out period should be allowed when used in successive trials with SSRIs or buspirone to avoid hypertensive crisis or serotonergic syndrome.
Pharmacological Augmentation Strategies
Many patients will require the addition of an augmenting drug. the double-blind placebo-controlled studies that established the efficacy of clomipramine and the SSRIs, reported that 40-60% of patients treated with one drug alone failed it achieve an adequate response the pharmacological strategy would involve choosing a different drug or an augmentation trial. If side-effects are mildly or moderately troubling, trying another drug is the more attractive option. If side effects are minimal, than a few augmentation trials are in order, and if successful, may bring about improvement more rapidly than starting a new SRI. Although controlled trials have been generally disappointing, case report literature are consistent with a modestly hopeful attitude in the individual case.

Table 2. Dose regimens for additional drugs used in treating OCD (Recommendation by the Expert Consensus Guidelines for Treatment of OCD (March et al.)
Medication Starting Dose Average target Maximum
Buspirone 20 60 90
Clonazepam 0.5 1-3 4
Gabepentin 300 1800-2400 3600
Haloperidol 0.25 0.25-6 6
Inositol 6 18 18
Lorazepam 0.5 1-6 6
Lithium 300 a a
Pimozide 0.5 1-6 6
Resperidone 0.5 0.5-5 6
Tryptophan 2 4-6 8
Venlafaxin 37.5 225-375 375
Buspirone : One in five or six patients show a significant response. The terget dose is 60-90mg/day in three divided doses. The trial is to be continued for six weeks at the maximum tolerated dose.
Clonazepam : Clonazepam is an unusual benzodiazepine in that if affects serotonergic systems and upregulates 5HT1 and 5HT2 receptor binding sites in the frontal cortex. A complex, double-blind cross over trial each given for six weeks, found Clonazepam, 4-10mg/day, as effective as clomipramine 175-250mg/day (Hewlett et al., 1992). But evidence for Clonazepam in monotherapy is still limited. But there fair evidence, when it is used as an augmenting agent. Patients with high levels of anxiety, agitation, insomnia or co morbid panic or bipolar disorder are good candidates for Clonazepam augmentation; depressed patients are not. Clonazepam response was not correlated with changes of anxiety. A four week trial at the maximum tolerated dose is adequate.
Neuroleptics : Neuroleptics may be an effective augmenting agent when OCD is accompanied by tics or frank tourette's syndrome. Lower doses are only required. It is important to start at the lowest possible dose and titrate the dose upward. There is little empirical support for the addition of a neuroleptic to an SRI for patients with co morbid cluster A personality disorder. But in case of co morbid psychosis it is prudent to start an adjunctive neuroleptic. An adequate trial of neuroleptic augmentation should last at least four weeks, and should be discontinued if there are no objective signs of improvement.
Gabapentin: Gabapentin when added to an SRI has shown mild to moderate improvement in anxiety, depression and OCD. Abrupt discontinuation is also reported to produce return of symptoms of greater intensity.
Lithium : Lithium enhances serotonergic transmission by several mechanisms. The positive results reported in OCD case series have not been mirrored in controlled trials. Overall the literature suggests that lithium augmentation is only occasionally beneficial although it can be effective for co morbid depression.
In addition, L-tryptophan, inositol, and fenfluramine have been reported in literature as adjuvants, they are currently unavailable in the Indian market, for various reasons including fatal side-effects. The safety and efficacy of their augmentation require more study.
Combination between SSRIs
Expert opinion, but no well-controlled trials support the addition of clomipramine to an SSRI with an inadequate response. If a trial of combining clomipramine and SSRI is elected, plasma levels of clomipramine and desmethylclomipramine have to be monitored; keeping a tab on pulse rates and BP is important; ECG is indicated if the patient is over 40 or has a preexisting cardiac lesion. Since monitoring drug levels is practically difficult, clinically a combination of fluvoxamine 75-150mg/day and clomipramine 100-150mg/day can be used to achieve adequate levels. Fluvoxamine inhibits the conversion of clomipramine to desmethylclomipramine, raising the levels of clomipramine 4 fold while keeping the levels of desmethylclomipramine low. The combination is well tolerated and has been effective in patients who have failed or been intolerant to clomipramine alone or multiple SSRIs alone.
Behavioural Treatment
Insight oriented psychotherapeutic approaches have been ineffective in eliminating or diminishing the incapacitating symptoms of OCD. The first hehavioural techniques used were disappointing; these techniques have evolved to more effective treatment strategies-exposure and response prevention (ERP)-the technique founded by Meyer in 1966. Only ERP in vivo has been found in multiple trials in OCD. Other techniques have been found effective in case series. A meta-analysis of ERP reported that an average of 76% of patients remained responders at a mean follow-up of 29 months.
Exposure in vivo brings the patient with contact with the feared object. Response prevention then blocks the ritualistic behaviour. Exposure was found to be more effective than response prevention in decreasing anxiety, but response prevention reduced rituals significantly more than did exposure. Imaginal exposure has been tried along with exposure in vivo, patients who receive a combination have been known to maintain gains for a longer period. Both modeling and flooding techniques are used for exposure in vivo. In participant modeling, the therapist first demonstrated the therapeutic procedure by making contact with the feared object and then asking the patient to follow suit. In flooding, the therapist does not demonstrate the targeted but encourages the patient into the feared situation. There are no differences in effectiveness between the two approaches. Type of response prevention has ranged from self-imposed response prevention to 24-hour supervision. There are no significant differences between patients receiving continuous supervision and patients with more minimal supervisory times. Patients who received prolonged exposure showed significantly more symptoms reduction compared with patients who received intermittent exposure. 20-30% of patients who fail to respond in spite of compliance have overvalued ideation and hold a strong conviction that their fears were realistic.
Behavioural treatment for obsessive ruminations
Patients with pure obsessions generally fare poorly with behavioural treatment. The common methods employed are Thought-stopping and Satiation.
Satiation involves exposing the patient to obsessional thoughts for prolonged periods until they loose their power to elicit anxiety. A convenient way to do this is to ask the patient to prepare a written script of his obsessions and then record it on a loop tape. The patient is exposed to it for a specified period each day.
Thought stopping involves teaching the patient to shout "STOP" mentally whenever he begins to obsess. The clinician begins by asking the patient to relax and then signal when obsessions begin. The clinician then loudly says, "STOP". The procedure is repeated number of times and the patient is encouraged to take over the responsibility for the verbal command, audibly at first, and later simply in the mind.
Cognitive techniques are becoming more widely used when there are predominant obsessions. It has been used not only to complement existing techniques but also as an alternative when patients refuse exposure. the most common faulty appraisals are overestimating the importance of thoughts; exaggerated responsibility for events; need to seek a perfect state such as absolute certainty or control; overestimation of the probability & severity of the consequences of action; and, consequences of anxiety. Specific strategies employed seek to change responsibility beliefs and appraisals, and thereby reduce distress and eliminate neutralizing responses which occur as covert mental rituals. The general style of therapy is that of guided discovery.
Schwartz (1996) recommends four cognitive steps, for which he has used the term "Brain Lock" approach. Patients are taught: to relabel the obsessive or compulsive experience as symptomatic of OCD rather than reflecting their essential selves; to recognize that the symptom is occuring because of brain activity rather than because of real external threats; to refocus their attention on something other than the immediate obsession or compulsion; and, to devalue the obsessive ideation as "worthless garbage".
Behaviour therapy has its limitations; one in four patients refuses to accept behaviour therapy or drop out early in treatment because of anxiety. Behaviour therapy fails in another 25% for a variety of reasons including concomitant depression; the use of central nervous system depressants; loss of insight; poor compliance with homework resulting in inadequate exposure; lack of skill in the therapist; thus overall around 50-60% of patients are helped by this form of therapy.
Maintenance treatment and discontinuation
Discontinuation of medication carries a high risk of relapse. 89% of patients who discontinued clomipramine after 5-27 months of successful treatment relapsed by the end of the seven weeks placebo period. Maintenance studies are consistent with these results. Implementing ERP therapy during the drug treatment may prevent or delay relapse, but this has not been firmly established. Patients can be successfully maintained on SRI doses substantially lower than those used during acute treatment. A gradual dose reduction of about 40% can be tried over a period of 1.5-2 years. If patients insist on discontinued in a gradual taper after 1-2 years, for the first episode and after 5 years, for patients with more than 3 episodes, after expa.
Treatment Resistant OCD
Treatment resistant OCD is defined as OCD which has less than 35% response to behaviour therapy plus at least 3 trials of SRI one of which is clomipramine in adequate doses and for adequate duration of time. Estimates of the proportion of patients who's OCD does not respond adequately vary from 20-40%.
Before labeling the patient as treatment strategies. When inadequate treatment is not the reason for poor treatment response, it is important to assess the accuracy of the diagnosis and further, for co morbidities.
For patients who are treatment resistant, the following general modes of intervention should be considered: augmentation strategies; behaviour therapies (both described earlier); alternative agents; alternative routes of administration; and, neurosurgical interventions. All these need to be administered in an inpatient or at least a partial hospitalization setting.
Alternative agents
Oral Morphine : Intermittent oral morphine can be tried in treatment refractory patients. Oral morphine 20-40 mg every five to eight days has been shown to have benefit in end-stage OCD without euphoric and physiological dependence in a single case series of patients.
Clozapine : Clozapine has been tried without effect in patients with refractory OCD. The ineffectiveness is also reported when patient have co morbid chronic motor tic disorder. Use of clozapine is un-indicated in OCD.
Trazadone : There are case reports of effectiveness of trazodone, especially in doses of 500 mg/day, but the evidence has not been replicated in double blind control trials.
In addition to the above drugs, MAOIs (phenelezine); resperidone; clonazepam; and, buspirone (all described earlier); have been tried as alternative monotherapies is resistant OCD.
Alternate routes of administration
Intravenous Clomipramine
Data from case series and a double blind, controlled trial suggest that intravenously administered clomipramine reduces OCD symptoms much more quickly than oral clomipramine and is better tolerated. Moderate to marked improvement was reported towards the end of 14 daily infusions. Though there was quicker improvement  in the intravenously administered group, at end point, the differences in improvement between the orally and intravenously administered groups were not statistically significant.
Intravenous Citalopram
Open trials have shown intravenous citalopram to be effective in resistant OCD. Intravenous citalopram showed rapid effectiveness in 60% of patients who had not responded to orally administered SRIs. The  effective doses ranged between 40-80 mg/day administered for 21 days. Further evidence from studies with a double blind design is warranted.
Neurosurgical Interventions
Expert opinion reserves consideration of neurosurgical interventions to treatment refractory, severely and chronically ill patients who have not responded to all conventional pharmacological and behavioural treatments. Frequently used criteria to refer a patient for psychosurgery are the following- Average duration of symptoms of 15 years; failure to respond to 5 years of systematic treatment minimum of two adequate medication trial with augmentation plus adequate behavioural therapy in the absence of severe personality disorder. The surgical procedures used-anterior capsulotomy, cingulotomy, and limbic leucotomy-all aim to interrupt the connection between the cortex and the basal ganglia and related structures. Data compiled from a number of small studies yielded a success rate of 55%-67% with this form of treatment. Post surgical risks have been minimized with current stereotactic surgical techniques. The introduction of the gamma knife for these procedures has further minimized side-effects.
Experimental Therapies
Transcranial Magnetic Stimulation
Right prefrontal transcranial magnetic stimulation has been shown to decrease compulsive urges in a case series. Further evidence is required for this modality of intervention which is still in the experimental stage.
Immunomodulatory Therapy
This modality of therapy is in the experimental stage for Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS). A number of variants have been tried including: plasmapheresis; Intravenous immunoglobulin; and, prednisolone. Response has been shown in case reports. Currently this modality should be tried only with caution.
Conclusion
OCD is a common disorder that can be debilitating. Fortunately first-line treatments, Namely SRIs and behaviour therapy (ERP) are at least partially effective for most patients. For those who fail first-line therapies, alternate pharmacological strategies include: augmentation of SRIs; non SRI monotherapies, or, intravenous administration of SRIs. It is important to keep in mind that the most effective augmenting tactic is to add concomitant ERP. In cases of severe, treatment unresponsive, chronic, and intractable OCD, Neurosurgical treatment may be indicated.
While researchers are searching for better treatments, it is important for clinicians to optimally utilize the tools currently available.