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Obsessive Compulsive Disorder (OCD) – A Primer on Neurobiology, Diagnosis and Treatment

Author: Dr. Sanil Rege MBBS, MRCPsych, FRANZCP

January 28, 2018

The hallmark of obsessive-compulsive disorder (OCD) is the presence of obsessions and compulsions. It has a bimodal incidence with peaks occurring in late childhood/early adolescence and again in early adulthood (20-29).

The lifetime prevalence of OCD is believed to be between 1% and 3%, and patients can experience chronic or episodic OCD symptoms throughout their lifetime. OCD is a time-consuming and distressing mental state that has higher disability-adjusted years than Parkinson’s disease and multiple sclerosis, combined making OCD one of the top 10 most disabling medical conditions. [1]

OCD is believed to diminish the quality of life of the patient similar in extent to those individuals with schizophrenia. [2]

OCD symptoms are time-consuming and distressing and are often accompanied with strong avoidance behaviours.

OCD is under-recognised, under-treated as well as frequently mistreated. We summarise the key diagnosis and treatment modalities in OCD based on the latest guidelines. [3], [4]

CLINICAL PRESENTATION AND DIAGNOSIS

Obsessions:

Persistent, unwanted, repetitive, intrusive thoughts, images and urges which are ego-dystonic and cause anxiety and distress

Compulsions:

Repetitive behaviours or mental acts performed in response to an obsession to reduce the anxiety or distress to prevent a feared consequence.


Screening

Recently validated screening tools include the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), which has good reliability and is widely used in clinical research.[5], [6]

However, utilising the Y-BOCS screening tool requires adequately trained medical staff to accurately assess the presence and severity of 64 unique obsessions and compulsions.

There are other screening tools that, although not as well validated, are still as reliable and sensitive. These include the obsessive-compulsive inventory short version (OCI-SV), which only takes 5 minutes to complete and has 18 items that are scored based on the degree of distress associated.

There is also, the Florida Obsessive-Compulsive Inventory, which has a 20-item checklist on a 5-choice scaling system.

Diagnosis

The diagnostic criteria and diagnostic interviewing for OCD are covered previously (see: Obsessive Compulsive Disorder – Diagnostic Interview).

An OCD diagnosis is based on clinical assessments of obsessive thoughts or compulsive behaviours that last more than one hour per day and are not the result of


a medical condition or substance abuse. Patients also do not have to show both obsessive and compulsive traits to be diagnosed as suffering from OCD.

The Diagnostic and Statistical Manual of Mental Disorders (5th edition) specifies OCD symptoms as clinically separate from delusions or persistent negative thoughts that may be associated with other psychiatric disorders such as depression or generalised anxiety.

The DSM-5 created a separate section called OCD and related disorders due to phenotypic, genetic, neuroimaging and treatment response data suggesting OCD and related disorders are a distinct entity.

The related disorders included are:

Body Dysmorphic Disorder Hoarding Disorder Trichotillomania Skin picking disorder Hoarding disorder Substance/medication-induced OCD OCD due to another medical condition

The ICD-11 consists of tic disorders, hypochondriasis and olfactory reference syndrome.

NEUROBIOLOGY OF OCD

The cortico-striatal-thalamic-cortical loop (CSTC) is considered the critical brain circuit involved in the phenomenology of OCD. The CSTC circuit plays an essential role in information processing.

According to Saxena et al., who proposed the model [7] –

OCD is mediated by an imbalance between the direct (excitatory, OFC-striatum-globus pallidus-thalamus-cortical) and indirect (inhibitory, DLPFC-striatum-globus pallidus-subthalamic nucleus-cortical) pathways within this circuit, which causes brain lock in the caudate nucleus and a mutual hyperactivation between the OFC and thalamus.

The imbalance indicates that the ‘brake’ that would control repetition is faulty.


Functional neuroimaging studies have shown increased activation in the areas of basal ganglia (predominantly head of caudate), anterior cingulate, and orbitofrontal cortex in OCD patients as compared to healthy controls. [8], [9]


Neurotransmitter systems in OCD

1. Serotonergic system 2. Glutamate – primary driver of the CSTC circuit 3. Dopamine – the direct and indirect pathway mentioned earlier consists of D2 and D1

receptors respectively, the imbalance of which affects the brake that controls repetition.

TREATMENT GUIDELINES

A recent clinical review attempted to outline the current guidelines on screening, diagnosis and treatment of OCD. [3]

This evidence review of the literature initially compiled 792 unique articles that consisted of randomised-controlled trials (RCTs), meta-analyses or systematic reviews. Of these 792 articles, 27 were selected based on the quality of evidence and their clinical importance.

PSYCHOTHERAPY

Although a systematic review and meta-analysis showed that cognitive behavioural therapy (CBT) has been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs), in clinical practice both SSRI’s and CBT are often used together. [10]

Both individual or group CBT are as effective as each other in the treatment of OCD with the most common psychotherapeutic approach being exposure-response prevention CBT (ERP-CBT).

Exposure-response prevention CBT is a structured form of psychotherapy whereby the patient is exposed to situations that would provoke the obsessions and associated anxiety and distress and then instruct the patient to resist the associated compulsions or avoidance behaviours.

The psychological mechanisms underpinning this technique are habituation and extinction.

Habituation is the decline in response after repeated exposure to a stimulus. Extinction refers to the cessation or reduction of behaviour when a reinforcer is taken

away or ceases.

Exposure-response prevention CBT is advised to have a frequency and duration of 13 to 20 weekly sessions or 3 weeks of daily sessions. If necessary, additional sessions can then be offered to the patient 3 to 6 months after the first session.

PHARMACOTHERAPY

SSRI’s


SSRI’s are considered the first line in the treatment of OCD.

Trials have shown no difference between any particular SSRI in treating OCD symptoms.

High dose SSRI’s have been shown to be more effective than lower doses. The medication and target doses are

Fluoxetine – 80mg/day Fluvoxamine – 300 mg/day Sertraline – 200 mg/day Paroxetine – 60 mg/day Citalopram – 40 mg/day Escitalopram – 40 mg /day

SSRI’s should be prescribed for at least 12 weeks to determine responsiveness.

Approximately 25% of patients with refractory OCD to SSRI’s may benefit from up to 28 weeks treatment after initiation.

SSRI’s should be prescribed for at least 6-12 months after response to prevent a relapse.

Clomipramine

The tricyclic antidepressant, clomipramine, has larger effect sizes for a response than SSRI’s.

It can be started at 25 milligrams per day. A target dose of 250 milligrams per day is recommended.

However, patient tolerability is poor due to significant anticholinergic side effects (dry mouth, blurred vision, fatigue, tremor and hyperhidrosis).

Therefore, based on safety data, clomipramine should instead be used as a second-line agent.

TREATMENT REFRACTORY OCD

Approximately 25% of all OCD patients will be classified as treatment-resistant: this is defined as failing two different SSRI courses.

Furthermore, 40-60% of all patients may be considered as responding positively to treatment but will have ongoing residual symptoms.


Antipsychotics

Augmentation with antipsychotics is effective in 30% of treatment-resistant patients. Haloperidol is an effective augmentation agent in OCD with comorbid tics.

Aripiprazole 5-10mg/day Risperidone 1-3mg/day Haloperidol 2.5-10mg/day Olanzapine 5-10 mg /day

NOVEL AGENTS

Glutamatergic agents

Memantine 10-20 mg/day Lamotrigine 100mg/day Topiramate 100-200mg/day N-Acetylcysteine 2400-3000 mg/day (Listen and read to Prof Berk’s talk on application

of NAC in OCD and other disorders) (see: Applications of N-Acetylcysteine (NAC) – From Addiction to Autism)

5 HT-3 Antagonists

Ondansetron (2-4 mg BD) and Granisetron (1mg BD)

Nutraceuticals

Myoinositol 5HT Milk thistle

NEUROMODULATION THERAPIES

Neurosurgery

Ablative neurosurgery involves producing lesions in specific regions of the CSTC circuit. Neurosurgery is indicated in only severe cases of OCD. Approximately 60 percent of patients improve 6-24 months post surgery.

Key techniques for surgery are:

anterior cingulotomy capsulotomy subcaudate tractotomy limbic leucotomy (combination of anterior cingulotomy & capsulotomy)

Deep Brain Stimulation:


Involves targeting the anterior limb of the internal capsule, nucleus accumbens, ventral caudate, thalamus, subthalamic nucleus and ventral striatum. A metanalysis showed a 60 percent response rate with DBS. [11]

rTMS:

The regions associated with OCD are not usually accessible by TMS. However, there is some evidence of efficacy.

COMORBIDITIES IN OCD

Depression [12]:

Depression is the most common comorbidity in OCD. We covered a case report on OCD and depression and how augmentation strategies can treat both OCD and depression (see: How to Treat Depression by Using Biological Deconstruction – Case Files of a Patient with OCD and Depression).

Depressive cognitions are ruminative and have an ego-syntonic quality with thought content revolving around guilt, self-criticality, self-doubt, nihilism, worthlessness and hopelessness.

Anxiety Disorders [12]:

Comorbid anxiety is associated with a poorer treatment outcome. Anxious thoughts are related to real life concerns and are not associated with

compulsions. SSRI’s are effective in the treatment of anxiety and OCD.

Bipolar Disorder:

In comorbid bipolar disorder, OCD can manifest with increases in severity in depressive episodes but improvement during manic/hypomanic episodes.

Mood stabilisers or atypical antipsychotics are considered the first choice of treatment. If OCD persists despite treatment with a mood stabiliser/atypical antipsychotic, then

SSRI’s can be used as an augmentation strategy. SSRI’s on their own may be associated with a worsening of underlying bipolarity.

Schizophrenia/Psychosis:

Individuals with schizophrenia have a significant incidence of OCD symptoms (25%). This association may be related to

the prodromal phase of psychosis neuroleptic-induced OC symptoms (atypical antipsychotic medications, e.g. clozapine,

risperidone and olanzapine can increase OC symptoms OCD occurring concurrently in psychosis Schizo-obsessive presentation [13]


SSRIs may be used in treating OCD comorbid with schizophrenia.

Personality Disorder:

Obsessive-compulsive personality disorder / Anankastic personality disorder is the most commonly associated personality disorder.

Excessive preoccupation with perfectionism, orderliness, and rigid control. Stubbornness, scrupulosity and over-conscientiousness are key traits.

Tic Disorders:

Presence of comorbid tics may predict a poor response to SSRI’s. Tic disorders show the best response to antipsychotics (haloperidol, pimozide,

risperidone and aripiprazole). Adrenergic α2 agonists (clonidine and guanfacine) are also evidence-based. Habit-reversal therapy (HRT) is a potential first-line treatment option instead of or in

combination with pharmacotherapy.

SUMMARY ALGORITHM


References 1. World Health Organization (WHO). The Global Burden of Disease: 2004 Update. Geneva, Switzerland: World Health Organization. 2008

2. Subramaniam M et al., Quality of life in obsessive-compulsive disorder: impact of the disorder and of treatment. CNS Drugs. 2013

3. Hirschtritt M et al., Obsessive-compulsive disorder: advances in diagnosis and treatment. JAMA Clinical Review and Education. 2017

4. Reddy, Y. J., Sundar, A. S., Narayanaswamy, J. C., & Math, S. B. (2017). Clinical practice guidelines for Obsessive-Compulsive Disorder. Indian journal of psychiatry, 59(Suppl 1), S74.

5. Goodman W et al., The Yale-Brown Obsessive Compulsive Scale I: development, use, and reliability. Archives of General Psychiatry. 1989


6. Goodman W et al., The Yale-Brown Obsessive Compulsive Scale II: validity. Archives of General Psychiatry. 1989

7. Saxena, S., Brody, A. L., Schwartz, J. M., & Baxter, L. R. (1998). Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. The British Journal of Psychiatry.

8. Parmar, A., & Sarkar, S. (2016). Neuroimaging studies in obsessive compulsive disorder: A narrative review. Indian journal of psychological medicine, 38(5), 386.

9. Nakao, T., Okada, K., & Kanba, S. (2014). Neurobiological model of obsessive–compulsive disorder: evidence from recent neuropsychological and neuroimaging findings. Psychiatry and clinical neurosciences, 68(8), 587-605.

10. Ost L et al., Cognitive behavioral treatments of obsessive-compulsive disorder: a systematic review and meta-analysis of studies published 1993-2014. Clinical Psychology Reviews. 2015

11. Alonso P et al., Deep brain stimulation for obsessive-compulsive disorder: a meta-analysis of treatment outcome and predictors of response. PLoS One. 2015

12. Nestadt G et al., The relationship between obsessive-compulsive disorder and anxiety and affective disorders: results from the Johns Hopkins OCD Family Study. Psychological Medicine. 2001

13. Bottas, A., Cooke, R. G., & Richter, M. A. (2005). Comorbidity and pathophysiology of obsessive–compulsive disorder in schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia?. Journal of Psychiatry and Neuroscience, 30(3), 187.

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