Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Is one atypical antipsychotic better than another?

  • In this case, the quetiapine-XR (Seroquel-XR) certainly is supported, given its approved status, clinical data evidence base, and indication for treating unipolar MDD adjunctively

  • However, its higher dose is out of the approved range for unipolar or bipolar depression (not for psychosis), but in this case was helpful

  • Aripiprazole (Abilify), brexpiprazole (Rexulti), or lurasidone (Latuda) has similar approvals and could have been used instead

    • As this patient came into treatment with certain metabolic illness problems, choosing a more metabolically friendly atypical antipsychotic like these may have been warranted initially

  • However, in her case she did not develop any metabolic worsening

• – No atypical antipsychotic has approval for treating OCD, but treatment guidelines support their adjunctive use in resistant cases

Possible action items for improvement in practice

• – Research clinical trials, off-label data for augmentation strategies for treatment-resistant OCD

• – Research-available US and international guidelines for OCD treatment, as these offer a summary list that is often easier to interpret, and provide a discussion regarding evidence-based treatments and the stringency of the available data

• – Review postpartum OCD as it is often under-recognized and undertreated

  • It is estimated that anywhere from 60% to 80% of new mothers will experience the “baby blues”

  • Postpartum depression is more severe and affects approximately 10%–20% of new mothers

  • Postpartum OCD affects approximately 3%–5% of new mothers

    • The focus of the obsessions is often on the fear of purposely harming the newborn, or somehow being responsible for accidental harm

• – If this patient’s contamination fear were actually paranoid and delusional in nature, finally achieving a reasonable dose of antipsychotic may have alleviated this and her other depressive symptoms

  • In this case, using a higher-dose atypical antipsychotic sooner may have been warranted

Tips and pearls

Treating OCD often requires very high doses of SSRI antidepressant agents

High doses often have to be maintained for several weeks to a few months to achieve clinical effectiveness

Failure of OCD to respond to high-dose SSRI may be augmented with atypical antipsychotics to gain further response or remission

Neurocircuitry moment

Why are OCD brains OCD?

Dysfunction in the orbitofrontosubcortical circuitry, composed of direct and indirect pathways from the frontal cortex and projecting into the striatum, are hypothetically implicated

The direct pathway

• – Projects from the striatum to the globus pallidus interna/substantia nigra, pars reticulate complex (the primary output location of the basal ganglia)

• – Back to the cortex, which activates the thalamic system

• – This generates, promotes, and coordinates complex motor activities

The indirect pathway

• – Follows a longer route starting from the striatum and continuing through the globus pallidus externa, subthalamic nucleus, globus pallidus–substantia nigra pars reticula, thalamus

• – Ultimately returning to the cortex

  • This is an inhibitory pathway that attempts to dampen complex motor activities

A mentally well-functioning brain would have a balance between these two pathways, allowing the correct amount of motor activity

OCD patients may show more activation of the direct pathway, thereby increasing activity in the OFC, ventromedial caudate, and medial dorsal thalamus, which could result in compulsive, repetitive behavior activity.

• – The indirect pathway appears unable to inhibit the more aggressive direct pathway’s activity, allowing compulsive behaviors to continue

The neurocircuitry of OCD and non-OCD anxiety disorders differs

• – OCD brains demonstrate dysfunction in the frontostriatal circuitry as noted here

• – Other anxiety disorders often involve the amygdala and a fear response component

• – This may explain why OCD tends to require higher doses and longer durations of treatment compared to other anxiety disorders as the neurocircuitry involved is dependent upon the disorder being treated

Two-minute tutorial

Figure 15.1. Obsessive compulsive disorder pharmacy.