Catherine Smith, PharmD, BCPS, BCPP, works for the Southern Arizona VA Medical Center (SAVAHCS) in primary care and outpatient mental health clinics. Her professional interests include geriatrics, deprescribing, and quality improvement. She received her PharmD from the University of New Mexico in 2019. Following her Ambulatory Care focused PGY-1 Pharmacy Practice Residency training at the Boise VA in Boise, Idaho; she completed a PGY-2 Psychiatric Pharmacy Residency at the Boise VA. Catherine joined SAVAHCS in 2023. She is the PGY1 residency program coordinator, primary preceptor for both PGY1 and PGY2 pharmacy residents in the severe mental illness (SMI) primary care rotation, PCMHI rotation, and is a co-editor of the patient newsletter.
Kristin Helmboldt, PharmD, BCPP, has worked at the Boise VA Medical Center for over a decade. She earned her Doctor of Pharmacy degree from Idaho State University and completed a mental health-focused pharmacy residency at the Boise VA Medical Center. With more than 25 years of experience in mental health pharmacy, Kristin brings a unique perspective shaped by 15 years as a Director of Pharmacy at a community acute psychiatric inpatient hospital prior to her time with VA. Her clinical interests focus on ADHD and the integration of non-pharmacological treatments for mental health disorders, reflecting a holistic approach to psychiatric care. Kristin was the PGY2-Mental Health program director for 5 years and has been a primary preceptor for both PGY1 and PGY2 pharmacy residents in the outpatient MH rotation, PCMHI rotation, and memory care rotation.
Systematic Thinking
Prescribing in clinical gray areas is not uncommon within behavioral health. There are no definitive biological tests (blood panel or scans) that can diagnose depression , anxiety, ADHD, etc. Diagnoses are based on symptoms through patient self-report and using clinical judgement. Many conditions share similar symptoms and can look similar, thus a practitioner may prescribe based on the most likely explanation while remaining uncertain. Diagnostic uncertainty is one kind of clinical gray area. Treatment-resistant conditions, concomitant medical conditions, age, resource scarcity and biopsychosocial factors can also lead to prescribing in clinical gray areas.
Regardless of a patient’s treatment history, a wise initial step is to review prior treatments in as much detail as possible. We do not assume that all previously prescribed medications constitute adequate trials and we may consider previously trialed medications. If a medication was poorly tolerated in the past, we look for reasons for poor tolerability during chart review and while discussing with the patient (i.e. Initial dose too high? Lack of appropriate expectations or follow-up?).
Pharmacogenomic testing may provide further insight into an individual patient’s metabolic profile. We use this information for dosing medicines, less so for treatment selection. The role and timing of pharmacogenomic testing in a patient’s treatment is evolving. Currently, access to testing varies based on practice settings.
At all stages we prioritize medications that may benefit multiple conditions and dual or triple benefit should always include trying to deprescribe or streamline a patient regimen. One example is the use of a tricyclic antidepressant for sleep, migraine prevention, and irritable bowel syndrome with diarrhea as well as depression.
The spectrum of prescribing in evidence gaps can range from highly evidence-based to lower levels of evidence. Once third-line guideline-recommended treatment options and/or all guideline-directed pharmacotherapies have been trialed or deemed inappropriate, we look at off-label treatment recommendations. For treatment-experienced patients, we consider medicines that have less evidence for treating a particular condition. A PubMed search of primary literature can help generate treatment ideas as can reaching out to colleagues with more clinical experience. In this context, we often reference case series and case reports because gold-standard studies like randomized controlled trials or meta-analyses are not available. We avoid utilizing AI for literature review or generating treatment ideas. If AI is utilized, it is critically important to review the primary literature cited by AI to ensure accuracy. We may also consider non-pharmacologic treatments (repetitive transcranial magnetic stimulation, alpha-stimulation, acupuncture). Depending on your workplace, non-pharmacologic treatments may be accessible earlier in a patient’s treatment course, and could be considered prior to last-line pharmacotherapies.
Shared decisions with patients
Behavioral health treatment goals can be subjective; we ask patients about their treatment goals and actively use these goals to assess treatment efficacy during medication management. This also gives us a way to have an open conversation about expectations and the opportunity to create reasonable, measurable expectations that are meaningful to our patients. Tolerability tends to improve when patients have reasonable expectations, so we encourage counseling on all common side effects, including at-home management of mild-to-moderate side effects and the anticipated time to benefit prior to prescribing. We find it supports patient adherence by setting expectations for side effects and time to benefit up front. We encourage providing patient counseling information in writing whenever possible so patients can reference it later.
When a patient is uncertain of trialing a medication that could be beneficial, we recommend a 4-to-6-week trial period. Framing a medication trial as a temporary change rather than permanent can encourage a patient to give it a try. We follow up frequently after initiating a new medication to assess tolerability and adherence.
In some cases, clinical gray areas arise when a patient has multiple comorbid medical conditions that restrict medication options. We recommend some extra time set aside for pre-visit chart review in these cases whenever possible.
We frequently reconcile medications, screen for drug interactions, and assess need for dose adjustment based on renal or hepatic function per manufacturer recommended monitoring guidance. We assess home blood pressure, heart rate and include electrocardiograms in our monitoring plan when appropriate. Monitoring may occur more often than manufacturers recommend if clinically indicated, particularly for medically complex patients.
Acknowledgement of uncertainty
Informed consent and documentation of off-label medication use is very important. Patients deserve to have a full explanation of your clinical rationale and the opportunity to accept or decline the suggested treatment.
We think it is important to recognize our limitations. Treatment-resistant cases may benefit from specialist consultation for further diagnostic clarity or ongoing medication management. It is important to feel comfortable referring to a higher level of care. We encourage you to view referral as a positive step rather than feeling like you’ve missed something or that you’ve failed your patient. Your attitude about these referrals will increase your patient’s confidence in the transition of care.
In conclusion, clinical decision-making in evidence gaps requires systematic thinking, shared decision-making between patient and provider, and honest acknowledgment of uncertainty. We hope the suggestions above are helpful in your practice.