Ability to:

1. Evaluate when response to initial pharmacotherapy, of sufficient dose and duration, is inadequate, or initial pharmacotherapy is not well tolerated because of side effects, and further increasing dose, changing to an alternate agent or adding an augmentation strategy is appropriate   Evidence: TG: Koran et al 2007

2. Select and implement a second-line treatment strategy after inadequate response to initial pharmacotherapy, taking into account response to initial treatment, available evidence, and patient preferences. • Switch to specialized CBT • Augment with specialized CBT • Increase dose of SSRI • Switch to a second SSRI • Switch from SSRI to clomipramine • Augment with secondary pharmacotherapy (e.g. neuroleptic) • Augment with a second serotonergic agent (e.g. clomipramine + SSRI)   Evidence: TG: Koran et al 2007, Koran and Simpson 2013 • MA: Skapinakis et al 2016a • OR: Fineberg et al 2016, Simpson 2017 • RCT: Foa et al 2005, Simpson et al 2008, Simpson et al 2013 • OCT: Wheaton et al 2016 Management of SSRI and clomipramine monotherapy is discussed in the section above. Specialized CBT is discussed in companion papers in this series (Sookman et al, 2021b; Piacentini et al, under review).

3. Assess the appropriateness of and implement neuroleptic augmentation of SSRI or clomipramine, recognizing that this is the pharmacological augmentation strategy best supported by available evidence   Evidence: TG: Koran et al 2007, Koran and Simpson 2013 • MA: Skapinakis et al 2016a • OR: Fineberg et al 2016, Simpson 2017

• Efficacy of neuroleptic augmentation, recognizing that data are strongest for risperidone, aripiprazole   Evidence: MA: Bloch et al 2006, Ipser et al 2006, Veale et al 2014, Dold et al 2015

• Choice of agent, recognizing that higher potency D2 antagonists may be indicated in patients with tics or a history of tics   Evidence: MA: Bloch et al 2006, Ducasse et al 2014, Veale et al 2014

• Dosing of neuroleptic augmentation, recognizing that low doses are typically indicated • Assessment of response, recognizing that response is typically more rapid than with the SSRIs (2–4 weeks) • Assessment of any side effects of neuroleptic treatment   Evidence: TG: Koran et al 2007

• Discontinuation of neuroleptic treatment when ineffective or limited by side effects   Evidence: OR: Maina et al 2003

4. Assess the appropriateness and implement the combination of an SSRI with clomipramine, acknowledging that the evidence base behind this strategy is very limited.   Evidence: TG: Koran et al 2007 • OCT: Ravizza et al 1996, Figueroa et al 1998, Pallanti et al 1999, Diniz et al 2010