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

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.

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 (5^th 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
• 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.

AUTOIMMUNE OCD

There is increasing evidence of the existence of a subset of OCD associated with infections and autoimmunity.

The following subsets have been described: [Endres et al, 2022].

• Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS): proposed to be caused by an infection with group A beta-hemolytic Streptococcus pyogenes.
• Pediatric acute neuropsychiatric syndrome (PANS): Other pathogens such as Mycoplasma pneumoniae, Borrelia burgdorferi, Borna disease virus, and Toxoplasmosis gondii as possible causes.
• Autoimmune encephalitis related OCD
• Neuropsychiatric involvement in Systemic autoimmune diseases : e.g. Systemic lupus erythematosus, Dermatomyositis, and Sjögren’s syndrome

Diagnostic criteria for PANDAS:

PANDAS can be diagnosed with all of the following symptoms (1–5) present:

1. Presence of OCD or a tic disorder
2. Prepubertal symptom onset
3. Acute symptom onset and episodic (relapsing-remitting) course
4. Temporal association between Group A streptococcal infection and symptom onset/exacerbations
5. Association with neurological signs (motor hyperactivity or choreiform movements

Red flags for suspicion of Autoimmune OCD:

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 SSRIs 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

SSRIs

SSRIs 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 SSRIs have been shown to be more effective than lower doses. The medication and target doses are

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

SSRIs should be prescribed for at least 12 weeks to determine responsiveness.

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

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

NOVEL AGENTS

Glutamatergic agents

• Memantine 10-20 mg/day
• Lamotrigine 100 mg/day
• Topiramate 100-200 mg/day
• N-Acetylcysteine 2400-3000 mg/day (Listen and read to Prof Berk’s talk on application of NAC in OCD and other disorders)

5 HT-3 Antagonists

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

Treatment for PANDAS / PANS: [Endres et al, 2022].

• Psychotherapy and psychopharmacological treatments are first line
• For treatment resistant patients anti-microbial agents (antibiotics, anti-virals and anti-parasitic agents)
• For moderate to severe symptoms: steroids or intravenous immunoglobulins (IVIGs).
• For severe or chronic presentations: prolonged steroid trials or repeated high-dose steroids may be indicated.
• For patients with extreme impairment: Therapeutic plasma exchange is the first-line therapy alone or in combination with IVIGs, high-dose intravenous steroids, and/or rituximab.
• Children with PANDAS who have a severe form and/or recurrent courses of streptococcus-associated exacerbations or an initial manifestation : Antibiotic prophylaxis.

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.
• 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.
• SSRIs 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 SSRIs can be used as an augmentation strategy.
• SSRIs 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]

Read more about the management of OC symptoms in 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 SSRIs.
• 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

QUIZ