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Clozapine in the Outpatient Setting: Why It Still Matters

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Drawing of large textbook with medications and written notes nearby.

Clozapine remains the most effective antipsychotic for treatment‑resistant schizophrenia, and recent Risk Evaluation and Mitigation Strategy (REMS) changes mean community-based providers are more likely to encounter patients starting or maintained on it, or be asked to co‑manage their care, given the shortage of mental health specialists in Washington. This overview focuses on what matters most in these care settings: when to think about clozapine, how monitoring has shifted, and the key safety pearls that will keep your patients out of trouble.

Clozapine is uniquely effective for patients with treatment‑resistant schizophrenia, typically defined as non‑response to at least two adequate antipsychotic trials from different classes over 4–6 weeks. About 30% of patients with schizophrenia meet this definition, yet U.S. prescribing rates are far below that, historically around 11% and declining, while countries like Australia approach 35% use among eligible patients.

The clinical benefit is not just symptom scores. Multiple meta-analyses indicate that clozapine reduces overall symptom burden, hospital bed days, and even mortality in comparison with the use of other antipsychotics. Surprisingly, given its substantial adverse metabolic effects, it even decreases deaths from ischemic heart disease in comparison to other antipsychotics. An influential publication by Tiihonen from 2009 following Finnish approximately 60,000 patients for 11 years indicated that clozapine had a 26% reduction in overall mortality.

REMS Changes: What’s Different Now

The most practice‑changing update is that the clozapine REMS program has been discontinued as of February 2025. Prescribers, pharmacies, and patients no longer need to enroll in a centralized registry managed by the FDA, and there is no longer a system‑level requirement to submit ANC values before dispensing.

However, the recommended Absolute Neutrophil Count (ANC) monitoring schedule in the prescribing information has not changed: weekly for 6 months, every 2 weeks for the next 6 months, then monthly indefinitely. The practical implication is a shift in responsibility—where pharmacists and a centralized database once served as a second set of eyes, the onus now falls almost entirely on the prescriber to ensure appropriate monitoring and interpretation of neutrophil counts.

For primary care clinicians asked to co‑sign labs, renew prescriptions, or cover during transitions of care, it is important to recognize that while administrative barriers are lower, the clinical risks of neutropenia and myocarditis remain, especially during the first 18 weeks and 4 weeks of therapy, respectively.

Neutropenia: Understanding the Real Risk

Early experience in Finland, where a cluster of agranulocytosis‑related deaths occurred in a single facility in 1975, cast a long shadow over clozapine’s reputation. Subsequent data suggested agranulocytosis occurs in approximately 0.4% of patients, with neutropenia rates somewhat higher, and around 550 deaths have been reported globally over decades. The highest risk period is during the first 6–18 weeks of treatment, after which risk falls sharply.

Large‑scale monitoring data from Australia and New Zealand (2.6 million ANC values) found that by 18 weeks, 0.9% of patients had a serious neutropenic event; from 25 to 50 weeks, only 16 additional events occurred, and from 50 to 100 weeks, only 20. Another long‑term Finnish study showed that after the first six months—when agranulocytosis risk was 36 times higher—risk in the following 2-3 overlapped with that seen with non‑clozapine antipsychotics. These findings underpin a major recent Delphi Consensus Guideline publication put out by an international group known as TRRIP or Treatment Response and Resistance in Psychosis Working Group suggesting that ANC monitoring could safely be reduced after 2–3 years in the future.

The FDA prescribing information for clozapine still suggests the following ANC monitoring frequency:

  • Weekly x first 6 months, Every 2 weeks for months 6-12 and Every 4 weeks thereafter.

However, the 2025 Delphi Consensus Guidelines suggest the following ANC monitoring frequency and many anticipate that the FDA will adjust the prescribing information to the following:

  • Weekly x first 18 weeks, Every 4 weeks from weeks 18-2 years, Annually thereafter.

For now, primary care pearls include:

  • Expect the most ANC events in the first 18 weeks-6 months; a sudden drop later in treatment is less common and more likely to be a minor neutropenic event but still warrants workup.
  • Treat fevers, sore throat, or infection‑like symptoms in a clozapine patient as a potential hematologic emergency until proven otherwise; checking an ANC promptly is appropriate.
  • Be aware that other countries (EU, Australia, New Zealand, Netherlands, Finland) often monitor weekly for 18 weeks then move to monthly, reflecting their interpretation of the early‑risk data.

During the COVID‑19 pandemic, UK and VA systems experimented with extending monitoring intervals (for example, every 12 weeks) and did not see increased neutropenia or hospitalizations, and patients on extended schedules were 31–49% less likely to discontinue clozapine. These real‑world data support a more flexible, individualized risk–benefit conversation, particularly for stable long‑term patients struggling with frequent lab visits.

Myocarditis: The Under‑Recognized Early Threat

Myocarditis is at least as important as neutropenia from a mortality standpoint and may warrant more vigilance from non‑psychiatric clinicians. Approximately 539 myocarditis‑related deaths have been reported worldwide, like agranulocytosis, but myocarditis carries a much higher case fatality rate—up to 50%, compared with about 2% for agranulocytosis.

Key clinical pearls for myocarditis:

  • Timing: Most cases occur in the first 3–4 weeks of treatment, rarely beyond 8 weeks.
  • Risk factors: Younger age (under 40) and aggressive titrations appear to increase risk.
  • Presentation: Symptoms are non‑specific and easily misattributed—fever, flu‑like illness, fatigue, malaise, tachycardia, and hypotension, followed by rising CRP, troponin, and eosinophilia.

A practical approach, especially in primary care settings co‑managing new starts, is to:

  • Monitor daily for non‑specific symptoms during the first month; patient and family education is critical.
  • Add weekly CRP and troponin for at least the first 4 weeks (up to 8 weeks in higher‑risk patients).
  • If CRP is 50–100 mg/L, increase monitoring and consider slowing the titration.
  • If CRP exceeds 100 mg/L or troponin is more than twice the upper limit of normal, stop clozapine and involve cardiology urgently.

From a primary care perspective, any new chest discomfort, disproportionate tachycardia, or “viral” picture in a newly initiated clozapine patient should trigger a low threshold for ECG, troponin, CRP, and cardiology consultation.

Titration, Levels, and What Providers Need to Know

Traditional inpatient titration starts at 25 mg/day and increases by 25 mg increments to reach roughly 300 mg by day 14. Emerging myocarditis data support slower up‑titration strategies, such as reaching 275 mg by week 4 (NHS example) or 100 mg by day 17 in Dutch protocols, with Dutch populations showing some of the lowest myocarditis rates.

Therapeutic drug monitoring is increasingly used to optimize dosing:

  • A clozapine level of at least 350 ng/mL is usually needed for meaningful antipsychotic response.
  • Literature now suggests a practical “target range” of 350–600 ng/mL; older upper limits of 1000 ng/mL are being revised down by many labs to 600 ng/mL based upon meta-analysis showing higher NNT for higher levels.
  • Many patients do well at 600–1000 ng/mL if they are clinically stable and not experiencing dose‑related adverse effects such as seizures, myoclonus, or severe sedation.

For outpatient care, the main use of levels is during:

  • Non‑response (“Is this a pharmacologic failure or just subtherapeutic exposure?”).
  • Suspected toxicity (for example, sedation, confusion, new seizures, especially around infections, changes in smoking or drug interactions).

Though you may not initiate clozapine in your practice, it may help to know that an apparently “high” dose may be entirely appropriate if corresponding levels and the patient’s clinical status support it.

High‑Yield Drug and Disease Interactions

Clozapine is highly sensitive to CYP1A2 activity and systemic inflammation, which means common primary care issues can destabilize levels. Priority interactions include:

  • Tobacco smoking: As few as 5 cigarettes per day can decrease clozapine levels by 30–50% via CYP1A2 induction; stopping smoking during a hospitalization or quit attempt can rapidly increase levels at the same dose.
  • Fluvoxamine: A strong inhibitor that can cause large level increases; sometimes used intentionally by specialists to boost levels but risky without close monitoring.
  • Estrogen‑containing oral contraceptives and high caffeine intake: Moderate CYP1A2 inhibition; case reports describe patients needing up to a 50% dose reduction after starting oral contraceptives.
  • Acute infection (for example, pneumonia, sepsis): Inflammatory cytokines suppress CYP enzyme production, leading to lower levels of CYP enzymes and higher clozapine levels; in one inpatient series, up to 60% of patients with infection required a clozapine dose reduction of 50% or more.

The clinical takeaway is that any change in smoking status, hormone therapy, caffeine consumption, or major infection should prompt you to consider what this is doing to the clozapine level and whether a dose adjustment or level check is needed.

How Health Care Providers Can Add Value

Even if you are not initiating clozapine yourself, you play a central role in keeping patients safe and maximizing benefit:

  • Reinforce adherence to ANC monitoring and help interpret results, especially early in therapy.
  • Maintain a high index of suspicion for myocarditis for the first 4 weeks and neutropenia in the first 18 weeks of treatment.
  • Actively manage smoking cessation, infections, and interacting medications with an eye on clozapine levels and side effects.
  • Collaborate with psychiatry on individualized monitoring schedules for stable, long‑term patients who may safely tolerate less frequent lab visits.

Many patients who have cycled through repeated hospitalizations and failed multiple antipsychotics can achieve durable stability on clozapine—holding jobs, living independently, and staying out of the hospital for decades. With the REMS barrier removed, outpatient care provider involvement will be increasingly important to ensure that more of these patients can access and safely remain on this uniquely effective medication.

References:

  • Northwood K, Myles N, Clark SR, et al. Evaluating the epidemiology of clozapine associated neutropenia among people on clozapine across Australia and Aotearoa New Zealand:  a retrospective cohort study. Lancet Psychiat. 2024; 11:  27-35.
  • Rubio JM, Kane JM, Tanskanen A, et al. Long term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics:  a nationwide cohort and case-control study in Finland. Lancet Psychiat. 2024; 11:  443-50.
  • Siskind D, Northwood K, Pillinger T, et al.  Absolute neutrophil count and adverse drug reaction monitoring during clozapine treatment:  consensus guidelines from a global Delphi panel. Lancet Psychiat. 2025; 2, 77-85.

Jennifer Jepsen, PharmD, BCPS

Jennifer Jepsen is a Clinical Pharmacist within Harborview Medical Center. She has specialized in inpatient psychiatric hospital practice and has worked at Harborview, Western State Hospital and Navos. She has also worked within a Collaborative Drug Therapy Agreement as a prescribing pharmacist within an outpatient mental health clinic as well as a pharmacogenetic lab. She is a board-certified pharmacist in pharmacotherapy with interests in pharmacogenetics and geriatrics. 

PCL Satisfaction Survey Feedback, 2025-2026

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Every summer, we ask community providers who’ve consulted the PCL over the past year to share their feedback and improvement ideas through an anonymous survey. In 2026, we received survey responses from providers in 22 counties across Washington. Thank you all for your time and thoughtful feedback.

Of those who responded to the survey,

  • 100% were satisfied or very satisfied with the time it took to connect to the PCL psychiatrist
  • 99% were satisfied or very satisfied with the recommendations they received
  • 98% said they would use the PCL again and would recommend the service to their colleagues
  • 97% indicated the consultation helped them care for a specific patient
  • 94% said the consult would help in the care of future patients

PCL Improvement Ideas

Can PCL consult notes be uploaded to Epic?

  • Since we no longer collect patient identifiers like name and date of birth, this is not possible.

It would be great if the PCL shared treatment algorithms or simple handouts as part of consultations.

  • PCL psychiatrists routinely share standardized scales and screeners with callers, and most of these tools are also posted on the PCL website Resources page except for those that require a clinical review with the psychiatrist. Also, we are only able to share screeners that do not have copyright protection. We do not maintain patient-facing materials because these would be very challenging and resource intensive to develop and maintain for the entire state. Our partners at ScalaNW have a robust library of patient care algorithms regarding medications for substance use conditions.

Can I consult with the same psychiatrist when calling back on the same patient?

  • Given the number of psychiatrists who cover the PCL, we can’t guarantee the same psychiatrist is available for repeat consultations. However, several years ago the PCL database was improved to automatically retrieve previous notes to allow the psychiatrist on duty an opportunity to review earlier recommendations, thus creating more care continuity.

Can the PCL offer psychotherapy supervision?

  • Unfortunately, even though many of the PCL psychiatrists have training and experience in psychotherapy, this is not something the PCL can offer on a consistent basis as not all our psychiatrists have experience with all the various types of therapy. Thus, our website notes this in our FAQs and in-scope/out-of-scope content.

It would be helpful to provide info for complex patients on establishing with a long-term psychiatrist.

  • We have a similar guide for our department’s Family and Caregiver Support and Training (FACTS) Program. Click here to access the “Choosing a mental health provider” page of the FACTS website. A reminder that nearly half of Washington’s counties do not have a practicing psychiatrist but telehealth has helped improve access for some patients. It can also be challenging to find providers who accept Medicare.

Enhancing Behavioral Health for Dementia Care: A Multi-Modal Approach to Neuropsychiatric Symptoms

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Illustration of healthcare providers working with older adult patients.

Primary care and mental health providers are the frontline for managing the complex interplay between physical health and neuropsychiatric symptoms (NPS). Whether it is the subtle onset of depression in an older adult or the disruptive agitation of a patient with advancing dementia, the burden on the patient, their caregivers, and the healthcare system is profound. This article provides a concise guide to non-pharmacologic strategies, medication safety, and recent therapeutic updates to help streamline your psychiatric consultations for the care of those with dementia.

1. The Foundation: Non-Pharmacologic Management

Before reaching for the prescription pad, non-pharmacologic interventions should be the first-line approach, particularly for depression, anxiety, and agitation. These strategies are not only evidence-based but also avoid the polypharmacy risks inherent in psychiatric medications.

For Depression: Focus on Behavioral Activation. Encourage patients and caregivers to schedule small, manageable activities that once brought them joy. Even a 10-minute daily walk can significantly impact mood. Walking outside in the morning can also provide light exposure which can help with circadian rythms which can help promote regular sleep-wake cycles. Where and when available, engaging in adult day programs or senior centers that provide dementia support groups or programming can be helpful for structure.   Socialization is one of the main pillars of care for those with dementia.

For Anxiety: Implement Structured Relaxation. Teach simple diaphragmatic breathing or “box breathing” during the visit and provide written instructions/online resources to practice/review. Caregivers may need to cue them to do the breathing or suggest “let’s do some breathing together.” Referral to Cognitive Behavioral Therapy (CBT) remains the gold standard for long-term anxiety management but may need to be modified for those with cognitive impairment and also may not be readily available to all patients. Where cognitive impairment is still mild, this can still be effective with modifications.  Identify other calming environmental changes (check temperature, use of white noise or calming music, or distracting with a conversation or activity can be helpful).  What is calming should be individualized to that specific person.

For Agitation/Aggression: Use Environmental Modification. Identify triggers—such as loud noises, poor lighting, or “sundowning” patterns. Use nightlights to help with sundowning. Maintain a consistent daily routine. Using “validation therapy” (acknowledging the patient’s feelings rather than correcting their reality) can de-escalate aggressive outbursts. Avoid confrontation. Avoid overscheduling and allow adequate rest between activities. Acknowledge and respond to requests. Educate caregivers about dementia by providing resources for education and support. Identify sources of pain, constipation, need to use the bathroom, hunger, or thirst. Urinary retention and constipation from medications and dental issues are common underrecognized contributors to behavior.

2. Medication Review: Protecting Cognition

Polypharmacy is a quiet thief of cognitive function. Many common medications possess anticholinergic properties that can induce or worsen “pseudo-dementia.” A partial list of common contributors:

Drug ClassExamples to ReviewImpact on Cognition
Antihistaminesdiphenhydramine, hydroxyzineConfusion, sedation, increased fall risk.
TCAsamitriptyline, nortriptylineHigh anticholinergic burden; worsens memory.
Benzodiazepines And “Z drugs:lorazepam, alprazolam, zolpidem, zaleplon, eszopicloneParadoxical agitation, amnesia, and gait instability.
GI Agentshyoscyamine, dicyclomineMay cause acute delirium in the elderly.

The American Geriatrics Society’s has a list of medications (the Beers list) that can impact cognition and contribute to things like falls.  These medications are recommended not to be used in geriatric patients.  Remember that it’s not always a single agent causing the issue but rather the synergy of multiple agents with cognitive side effects.  Never abruptly stop medications; provide instructions for taper and discontinuation.  Regularly review and encourage patients and families to keep an updated list of all medications they take, who prescribes them, and include supplements and over the counter medications.  It is especially important to carefully review lists during transitions like a move or discharge from a hospitalization. For those in facilities, regularly review the Medication Administration Record (MAR) not just the orders list; the MAR documents scheduled medications but also how often as needed medications are being given and efficacy, which is especially important if as needed psychotropic medications are being prescribed.  Assessing from documentation whether a specific target symptom is improved with as needed medication administration is paramount so that ineffective medications are not given indefinitely.

3. Updates in Pharmacotherapy: Brexpiprazole and Pimavanserin

In 2026, the landscape for managing agitation associated with dementia shifted toward more targeted agents with improved safety profiles compared to traditional antipsychotics.

  • Brexpiprazole: Originally an adjunct for MDD and schizophrenia, brexpiprazole is now FDA-approved for agitation associated with Alzheimer’s dementia. It acts as a partial agonist at D2 and 5-HT1A receptors. Unlike older agents, it has lower intrinsic activity at dopamine receptors, which may reduce the risk of extrapyramidal symptoms (EPS).
  • Pimavanserin: This is a selective serotonin inverse agonist (SSIA) targeting 5-HT2A receptors. It is notably the only medication FDA-approved for Parkinson’s disease psychosis. Its lack of dopamine D2 blockade is critical because it treats hallucinations and delusions without worsening motor function.
  • Both medications are new and therefore can be quite expensive, often necessitating prior authorization/review of prior failed medications or justification for use.

The Role of Medications for the Treatment of Dementia

While not primary treatments for agitation, Acetylcholinesterase Inhibitors (AChEIs) like donepezil and NMDA receptor antagonists like memantine should be optimized. AChEIs can subtly improve apathy and anxiety, while memantine may help reduce the “overflow” of glutamate that contributes to irritability and aggression in moderate-to-severe cases.

4. Other antipsychotics: Considerations for Use and the “Black Box”

Antipsychotics (e.g., quetiapine, risperidone, haloperidol, aripiprazole) are frequently used off-label in primary care and in psychiatry for management of neuropsychiatric symptoms in dementia. Common reasons for use include:

  1. Acute Safety: When a patient is a danger to themselves or others.
  2. Severe Psychosis: Distressing hallucinations or paranoid delusions.
  3. Refractory Agitation, Inconsolable or persistent distress, or difficulty receiving care: When non-pharmacologic and first-line agents fail

FDA Black Box Warning: All antipsychotics (both typical and atypical) carry a “Black Box” warning regarding an increased risk of death in elderly patients with dementia-related psychosis. Most deaths are cardiovascular (heart failure, sudden death) or infectious (pneumonia) in nature. Informed consent with family and caregivers is mandatory before initiation.

Be aware of the particular risks of using many antipsychotic medications in those with dementia with Lewy bodies or dementia due to Parkinson’s disease as they can be exquisitely sensitive to extrapyramidal side effects. Quetiapine, pimsvanserin, or sometimes clozapine are first line agents where antipsychotic medications are needed. Brexpiprazole may be another option given its potentially lower propensity for EPS.

5. Supporting the “Invisible Patient”: The Caregiver

Caregiver stress is often an underrecognized contributor to symptoms in patients with dementia.  When a caregiver’s mental health fails, the patient’s institutionalization can become imminent and crisis-driven so it’s important to check in regularly.

  • Screening: Use the Zarit Burden Interview or simply ask: “How are you holding up?”
  • Depression in Caregivers: Caregivers have significantly higher rates of clinical depression than the general population. PCPs should treat the caregiver as an essential component of the patient’s “care ecosystem.”
  • Resources: Emphasize respite care. Encourage them to utilize local Area Agency on Aging resources to prevent burnout.

Managing psychiatric symptoms in dementia requires a delicate balance between behavioral interventions and careful medication management. Prioritizing non-pharmacologic strategies, reviewing cognitive-impairing drugs, and staying updated on new developments in pharmacotherapy are central management strategies for individualized dementia care.

Resources:

UW Medicine Project ECHO Dementia (virtual)
Free case-based learning for primary care providers hosted by dementia specialists at the UW; meets every other Friday; CME/CNE credit available.

Dementia Road Map
The DSHS Health Care Providers and Community Organizations page hosts clinical tools from the Dementia Action Collaborative, including the Dementia Road Map, a free guide for newly diagnosed patients and families.

Washington Association of Area Agencies on Aging
Connects adults with dementia and their families with local long-term care, community resources, and specialized caregiver support.

The Memory Hub, UW Medicine Memory and Brain Wellness Center
Offers education, support groups, and resources for patients and their care partners, including virtual or phone appointments with a Memory Navigator.

Alzheimer’s Association Washington State Chapter, Education and Resources
Free on-demand webinars and live programs on Alzheimer’s and dementia and a 24/7 Helpline for patients and families.

American Geriatrics Society Beers Criteria® Alternatives Panel, & Steinman, M. A. (2025). Alternative treatments to selected medications in the 2023 American Geriatrics Society Beers Criteria®. Journal of the American Geriatrics Society, 73(9), 2657–2677. https://doi.org/10.1111/jgs.19500

Brody, H., & Heath, A. (2023, July). Nonpharmacologic approaches to adverse behaviors associated with dementia. Practical Neurology. https://practicalneurology.com/diseases-diagnoses/alzheimer-disease-dementias/nonpharmacologic-approaches-to-adverse-behaviors-associated-with-dementia/32015/

Imbimbo, C., Cotta Ramusino, M., Leone, S., et al. (2025). Emerging pharmacological approaches for psychosis and agitation in Alzheimer’s disease. CNS Drugs, 39(2), 143–160. https://doi.org/10.1007/s40263-024-01133-9

Whitney Carlson, MD

Dr. Carlson is a board-certified psychiatrist and geriatric psychiatrist in the UW Medicine Department of Psychiatry and Behavioral Sciences. She graduated from the University of Iowa College of Medicine, completed her Psychiatry Residency at the University of Michigan and a Geriatric Psychiatry Fellowship at the University of Washington. Dr. Carlson is the medical director of the Geriatric Psychiatry Services Clinic at Harborview Medical Center and is one of the primary faculty on the Psychiatry Consultation Line (PCL). Her clinical interests include aging in chronic mental illness, mood disorders, nursing home psychiatry/consult liaison psychiatry, ethics, and palliative care.

Hormones and women’s mental health: a lifespan perspective

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Illustration of hormones surrounded by various treatment options.
Illustration of a honeycomb pattern representing hormones surrounded by various treatment options.

From menarche to menopause, the female reproductive lifespan is characterized by shifts in hormones that can influence mental health and lead to gender-based differences in prevalence, presentation and treatment considerations including in mental health care. For example, there is a clear increase in the incidence of depression in females beginning in puberty, which lasts throughout the lifespan. It is important to remember that while fluctuating reproductive hormones do contribute to increased rates of depression in women, it is driven by a complex interplay of biological and sociocultural factors.

In this article, we will review the mental health implications of fluctuations in reproductive hormones within a single menstrual cycle, and at physiological milestones such as menarche, pregnancy and perimenopause.

Menstrual cycles and mental health

Premenstrual syndrome (PMS) affects approximately 20% of menstruating individuals during the luteal phase (second half of the menstrual cycle from ovulation till onset of menses), and can be diagnosed by the presence of somatic (breast tenderness, bloating, headache, joint/muscle pain, weight gain, extremity swelling) or behavioral (fatigue, insomnia, food cravings, changes in sexual interest) symptoms with or without affective symptoms. 80 – 95% of reproductive-aged women experience at least one premenstrual symptom during the luteal phase.

Premenstrual dysphoric disorder (PMDD) affects a subgroup of women (prevalence 2 – 4%) who experience severe mood lability, irritability, dysphoria, anxiety and suicidal ideation during the luteal phase. Symptoms cause clinically significant distress and marked impairment in functioning and resolve within a few days of onset of menses.

Premenstrual exacerbation (PME) is the worsening of symptoms of an existing psychiatric condition during the luteal phase – symptoms are present throughout the cycle but become significantly more severe during the premenstrual and perimenstrual phases. About 60% of women with mood disorders experience PME, with a distinct pattern in bipolar disorder (where exacerbations may also occur around ovulation). PME also occurs in psychotic disorders, panic disorders, eating disorders, attention-deficit/hyperactivity disorder and borderline personality disorder. PME predicts a more severe course of illness and increased burden of illness as well.

In your practice, prospective daily symptom charting using the Daily Record of Severity of Problems (DRSP) can confirm whether symptoms are confined to the premenstrual window (PMDD) or represent a premenstrual worsening of a continuous disorder (PME). Consider providing this tool to patients presenting with cyclic mood symptoms.

Approximately one in five women of reproductive age is affected by either PMS or PMDD, yet these disorders are frequently undertreated. Treatment for PMDD includes SSRIs – continuous or intermittent (starting 1 week before menses and ending 3 days after onset) and combined oral contraceptives (COCs).

Treatment of PME involves optimizing treatment of the underlying condition and augmentation of the dosage of the existing treatment during the luteal phase. For example, for PME of unipolar depression, increasing the antidepressant dose during the luteal phase and returning to the baseline dose after menses can help. For bipolar disorder, the first step would be to optimize mood stabilizer dosing, and then address any remaining premenstrual symptoms with COCs, using SSRIs if needed with caution. Lamotrigine appears to specifically stabilize fluctuation of mood across the menstrual cycle. Preliminary studies indicate that individualized stimulant dose increases 3 – 10 days prior to menstruation can significantly improve focus in women with PME of ADHD.

Hormonal contraception (HC) and mental health

This is a topic of long-standing debate. Approximately 16% of women experience mood worsening with hormonal contraception. Danish cohort studies examined this issue and found

  • Higher relative risk of antidepressant initiation among HC users, particularly adolescents aged 15-19 compared to non-users.
  • Higher risk for suicide attempts and completed suicide among HC users compared to non-users.

While these data are sobering, mood disorders are not necessarily a contraindication to HC. Individuals with a history of depression should be attentive to potential mood changes after starting a hormonal contraceptive, with closer monitoring in adolescents. COCs with anti-androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms.

Managing interactions

Ethinyl estradiol can significantly reduce serum levels of lamotrigine and valproate by inducing the glucuronidation pathway. Women who are stable on lamotrigine and then start a COC may need their dose increased, and those who stop a COC while on lamotrigine will need to be monitored as their lamotrigine levels may suddenly rise.

Perinatal mental health

The perinatal period of course is a period of profound hormonal change and subsequent vulnerability to psychiatric illness. Most extensively studied are the hormonal underpinnings of postpartum depression (PPD). A subset of women appears to be sensitive to changes in the levels of estradiol and progesterone and following the acute hormonal withdrawal in the postpartum period, mood disturbance is triggered. Particularly important is the neuroactive progesterone metabolite allopregnanolone, a positive allosteric modulator of GABA-A receptors. Zuranolone is a formulation of allopregnanolone that is FDA approved specifically for the treatment of PPD.

Perinatal hormonal shifts may also influence the onset and course of other psychiatric conditions, including obsessive-compulsive disorder, post-traumatic stress disorder, and, rarely, postpartum psychosis although these are less studied.

Perimenopause and mental health

Perimenopause can last 4 – 8 years and is another period of intense hormonal flux. The risk of depression more than doubles at this time, again driven not only by rapid fluctuations in estradiol, but also by physical symptoms of perimenopause such as severe hot flashes, night sweats and subsequent sleep disturbance, and sociocultural stresses of caregiving, role transition and cultural attitudes toward aging. The risk of perimenopausal depression is higher in those with a history of postpartum depression or PMDD.

Treatment strategies include SSRIS, SNRIS, hormone replacement therapy or menopausal hormone therapy (MHT) – estrogen (combined with progesterone for those with an intact uterus) – and Cognitive Behavior Therapy for Insomnia. Although MHT is not considered a first-line treatment, estradiol may have antidepressant and anxiolytic effects in some perimenopausal women, and MHT may be useful in women who have a partial response to traditional antidepressants and those with significant vasomotor symptoms. Collaboration between psychiatrists, gynecologists and primary care providers can help create a comprehensive treatment plan. In 2025 the broad black box warning about cardiovascular disease and breast cancer associated with MHT was removed. MHT has several benefits when applied to appropriately selected women (e.g., under the age of 60 if they are within 10 years of their last menstrual period), including treatment of vasomotor symptoms and prevention of bone loss and fractures.

Ideally, our approach to women’s mental health would be informed by the shifting hormonal landscape across the lifespan — from puberty and the menstrual cycle, through pregnancy and the postpartum, to the menopausal transition — and interventions would be tailored based on the biopsychosocial context of each stage.

Resources:

For providers with questions about caring for patients in the perinatal period, please call the Perinatal PCL at 877-725-4666, Monday – Friday, 9 am to 5 pm (excluding holidays)

UW PERC Center Hormones and Mood Care Guide

The 20203 Practitioners Care Guide for Managing Menopause

Menopause Society Patient Education

References:

Arnold, M. J. (2024). Premenstrual Disorders: Guidelines From the American College of Obstetricians and Gynecologists. American Family Physician, 110(6), 647-650.

Faubion, S. S., Crandall, C. J., Davis, L., El Khoudary, S. R., Hodis, H. N., Lobo, R. A., … & Wolfman, W. (2022). The 2022 hormone therapy position statement of the North American Menopause Society. Menopause, 29(7), 767-794.

Jespersen, C., Lauritsen, M. P., Frokjaer, V. G., & Schroll, J. B. (2024). Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews, (8).

Kuehner, C., & Nayman, S. (2021). Premenstrual exacerbations of mood disorders: findings and knowledge gaps. Current psychiatry reports, 23(11), 78.

Wieczorek, K., Targonskaya, A., & Maslowski, K. (2023). Reproductive hormones and female mental wellbeing. Women, 3(3), 432-444.

Amritha Bhat, MD

Dr. Bhat is a perinatal psychiatrist and Associate Professor in the UW School of Medicine Department of Psychiatry and Behavioral Sciences where she serves as co-director of the Perinatal Mental Health & Substance Use Education, Research & Clinical Consultation (PERC) Center and the Perinatal Psychiatry Consultation Line (Perinatal PCL). Dr. Bhat earned her medical degree from Bangalore Medical College, India, and completed a psychiatry residency in St. John’s Medical College, India. She completed a second residency in Psychiatry with a focus on women’s mental health and integrated care from the University of Washington, and a fellowship in Primary Care in Psychiatry. Dr. Bhat also earned a master’s in public health from the University of Washington School of Public Health and is board certified with the American Board of Psychiatry and Neurology.

Beyond the Basics: Navigating Treatment Resistant Depression

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A blue graphic illustration shows a heart and brain divided, with medical icons like a cross and pulse line, symbolizing health and well-being.

Treatment-resistant depression (TRD) is one of the most significant challenges in modern mental healthcare. Far from being an outlier, evidence suggests that failing to achieve remission after an initial antidepressant trial is the norm, not the exception. The landmark STAR*D trial revealed that only about one-third of patients achieve remission with their first medication. This reality requires clinicians to have a robust, evidence-based framework for navigating next steps when initial treatments fall short. This article distills key clinical pearls for managing TRD, from reassessing the diagnosis to implementing effective augmentation strategies.

Defining the Challenge and the Importance of Measurement

A common working definition for TRD, derived from clinical trials, is an inadequate response to at least two adequate medication trials. The key word here is “adequate.” An adequate trial is defined by three critical factors:

  1. Duration: Has the patient been on the medication for a sufficient period, typically at least six weeks?
  2. Dose: Has the medication been titrated to a therapeutic dose? This doesn’t always mean the maximum dose, but one that is typically effective.
  3. Adherence: Is the patient taking the medication consistently as prescribed?

Before identifying a person’s depression as treatment -resistant, it’s crucial to confirm that each of these conditions has been met.

Consistent, objective measurement is the cornerstone of effective depression treatment. Implementing measurement-based care, most commonly with the Patient Health Questionnaire-9 (PHQ-9), is essential. Administering the PHQ-9 at every medication management visit provides an objective benchmark for progress, helps identify treatment resistance early, improves patient outcomes, and increases remission rates. It transforms a subjective report into actionable data, guiding clinical decisions with greater precision.

Re-evaluating the Foundation: Diagnosis and Comorbidities

When a patient isn’t responding to treatment, the first step is to reconsider the fundamentals. Are you treating the right condition?

  • Correct Diagnosis: Persistent depressive symptoms may point to an underlying condition that requires a different treatment approach. It’s vital to screen for bipolar disorder (assessing for any history of mania or hypomania), schizoaffective disorder, anxiety disorders, PTSD, and substance-induced disorders. Personality traits, such as those seen in borderline personality disorder, can also complicate treatment.
  • Comorbid Medical Conditions: Unaddressed medical issues can mimic or exacerbate depression. Always consider screening for conditions like sleep apnea, thyroid dysfunction (both hypo- and hyperthyroidism), and chronic pain, as treating these can significantly improve mood symptoms.
  • Substance Use: Ongoing use of substances—including alcohol, benzodiazepines, opioids, and cannabis—can significantly reduce the effectiveness of antidepressants and contribute to a depressive clinical picture.

The Central Role of Shared Decision-Making

Once you’ve confirmed the diagnosis and addressed comorbidities, the question becomes: what’s next? The evidence points to several viable options, including switching medications, augmenting with another medication, or adding psychotherapy. The most effective path forward is determined through shared decision-making.

Instead of searching for a single “best” option, the clinician’s role is to curate a few of the most reasonable, evidence-based choices and present them to the patient. Discuss the risks, benefits, and practicalities of each. When patients are actively involved in choosing their treatment path, we see improved satisfaction, engagement, and, most importantly, better adherence and clinical outcomes. This collaborative process honors patient autonomy and leverages the psychological benefit of being invested in one’s own care plan.

Augmentation: The Preferred Next Step

A significant shift in TRD management is the growing evidence supporting augmentation over switching antidepressants after a first failed trial. Augmenting—adding a second agent to the existing antidepressant—often leads to faster and higher rates of remission.

When pursuing augmentation, a key principle is to avoid polypharmacy. The goal should be a simple, two-medication regimen. If you find yourself prescribing three or more medications to treat a patient’s depression, it’s a critical moment to pause, re-evaluate the role of each agent, and seek consultation.

A Hierarchy of Augmentation Strategies

  1. Add Psychotherapy (when/if available): Consider adding therapy. Augmenting medication with an evidence-based psychotherapy like Cognitive Behavioral Therapy (CBT) is highly effective for TRD. A crucial long-term benefit is that skills learned in therapy lead to a lower risk of relapse after treatment discontinuation compared to medication alone. CBT via telehealth can be as effective as therapy delivered in-person. Telehealth may open up some options for patients.
  2. Augment with a Second-Generation Antipsychotic (SGA): There is robust and consistent evidence for the efficacy of SGAs as augmenting agents. Aripiprazole has the most extensive evidence base and often shows a greater effect than other options. However, this efficacy can come with a higher side effect burden, including akathisia. For patients who prioritize rapid symptom relief and are willing to tolerate potential side effects, this is a top-tier choice. If akathisia is a concern, brexpiprazole may be a better-tolerated alternative. Both medications have an FDA indication as adjunct treatment, but not monotherapy, for major depressive disorder.
  3. Augment with Another Antidepressant: Adding an antidepressant from a different class, such as bupropion or mirtazapine, is another effective strategy. Studies show this approach is nearly as effective as SGA augmentation but often with better tolerability and fewer side effects. This makes it an excellent option for patients who prioritize minimizing side effects.
  4. Consider Lithium: Lithium is a classic and effective augmentation agent, particularly valuable in patients with significant suicidal ideation due to its unique anti-suicide properties. However, the need for lab monitoring, as well as some specific risks (renal, thyroid, teratogen, etc.), place it further down the list for many clinicians, often considered after two different augmentation trials have failed.

Switching Antidepressants

Switching antidepressants typically involves trying a different antidepressant from a different class of antidepressants. Choosing from that new class of antidepressants is going to follow a similar strategy as outlined in last month’s newsletter on initial antidepressant selection and comes down to side effect profile, prior response, or comorbidities. Gene-drug interaction testing can provide additional insights into suggesting other options after two or more failed trials, but there is no guarantee for effectiveness. Switching from a low or moderate dose from a serotonergic medication to another serotonergic medication can be done rapidly by exchanging the old medication for an equivalent dose of the new antidepressant. Outside of that, a cross-taper method is preferred.

Advanced Treatments for Refractory Cases

When multiple medication and therapy trials have been unsuccessful, it’s time to consider neuromodulation.

  • Transcranial Magnetic Stimulation (TMS): TMS is a non-invasive procedure with a solid evidence base for TRD. It is often covered by insurance after two or more failed medication trials and is a comfortable, well-tolerated procedure that can be highly effective.
  • Electroconvulsive Therapy (ECT): For severe depression, particularly cases involving psychosis, catatonia, severe functional impairment, or acute suicidality, ECT remains the gold standard and should be strongly considered.

By adopting a systematic approach grounded in measurement, diagnostic diligence, and shared decision-making, clinicians can confidently and effectively guide patients through the complexities of treatment-resistant depression toward remission and recovery.

And remember, the UW Psychiatry Consultation Line (PCL) is always a resource to support you in the care of your adult patients with depression or any other mental health or substance use conditions. Prescribing providers can call any time, 24/7, and non-prescribing providers can call Mon-Fri, 8 a.m. – 5 p.m. (excluding holidays). 877-WA-PSYCH/877-927-7924 We are here to help!

To see Dr. Duncan’s complete UW PACC presentation on this topic, click on this link: Treatment Resistant Depression

Mark Duncan, MD

Dr. Duncan, trained in both family medicine and addiction psychiatry, practices at the intersection of mental health and primary care. He is the co-medical director for the University of Washington Psychiatry and Addiction Case Conference (UW PACC), a weekly online learning collaborative to help community providers across the state improve their psychiatric and addiction clinical skills. Dr. Duncan is one of the PCL’s core weekday faculty where his unique expertise in primary care and psychiatry is available to healthcare providers across Washington.

Back to Basics: A Refresher on Treating Major Depressive Disorder

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Major Depressive Disorder (MDD) remains one of the most common and impactful conditions seen in primary care. While many of us treat depression daily, it is valuable to periodically revisit the foundational principles of diagnosis and initial treatment to ensure we are offering the best possible care.

This article highlights key takeaways and “clinical pearls” from a recent presentation on the initial treatment of MDD. For those interested in a deeper dive, a link to the full transcript is provided at the end of this article.

Diagnosis: Beyond the Checklist

The DSM-5 criteria for a Major Depressive Episode are familiar to most: five or more symptoms present for at least two weeks, representing a change from previous functioning. One of the symptoms must be either depressed mood or loss of interest/pleasure (anhedonia).

However, beyond the checklist, pay attention to functional impairment. Is the patient calling in sick to work? Withdrawing socially? Spending excessive time in bed? These behavioral changes are often the most reliable indicators of severity.

The PHQ-9 as a Clinical Tool The PHQ-9 is not just a screener; it maps directly to DSM-5 criteria and can support your diagnosis. It is also the standard for measurement-based care to track symptoms and response to treatment over time. Initially, the total score helps stratify severity and guide treatment selection:

  • 5-9 (Mild): Consider psychotherapy or behavioral activation first.
  • 10-14 (Moderate): Psychotherapy, medication, or both are reasonable initial options based on patient preference.
  • 15-19 (Moderately Severe) & 20+ (Severe): Combination treatment (medication + psychotherapy) is often the gold standard.

Don’t Forget the Differential Before initiating treatment, rule out common mimics:

  • Medical causes: Hypothyroidism (TSH), anemia (CBC), vitamin deficiencies (B12, Folate, Vitamin D), and obstructive sleep apnea (OSA). Treating OSA can often resolve depressive symptoms entirely.
  • Substance use: Alcohol and cannabis are frequent contributors.
  • Bipolar Disorder: Screening for mania/hypomania is critical before starting an antidepressant. Use the Mood Disorder Questionnaire (MDQ) to reduce the likelihood of triggering a manic episode. The MDQ can be self-administered or administered with a provider. If the MDQ is negative, you can feel reassured that the likelihood of triggering a manic episode is unlikely. However, if it is positive, you will need to review the results to clarify the diagnosis as false positives are common.

Initial Treatment Selection

For mild to moderate depression, psychotherapy (CBT, Behavioral Activation) is as effective as medication and has lasting benefits. For more severe cases, or when therapy is inaccessible, pharmacotherapy is indicated.

Choosing an Antidepressant Most first-line agents (SSRIs, SNRIs, Bupropion, Mirtazapine) have comparable efficacy across the population. Therefore, selection should be driven by:

  1. Side Effect Profile: Leverage side effects to the patient’s advantage.
    • Insomnia + Weight Loss? Consider Mirtazapine (sedating, increases appetite).
    • Low Energy + Smoking + No anxiety? Consider Bupropion (activating, helps cessation, may worsen anxiety).
    • Sexual Dysfunction Concern? Bupropion and mirtazapine have a lower risk than SSRIs and SNRIs
  2. Prior Response: If it worked before (for the patient or a family member), try it again.
  3. Comorbidities:
    • Chronic Pain? Duloxetine (SNRI) has an FDA indication for certain kinds of pain.
    • Anxiety? SSRIs are generally preferred.

Initiating and Monitoring Treatment

Start Low and Go Slow: Minimize initial side effects to improve adherence. Titrate every few weeks until you reach a therapeutic dose or see a response.

The 4-6 Week Rule: An adequate trial is typically 4-6 weeks at a therapeutic dose.

  • No response? Switch to a different medication (different SSRI or different class).
  • Partial response? Consider augmentation (e.g., adding Bupropion, Mirtazapine, or a second-generation antipsychotic like aripiprazole).

Duration of Treatment: For a first episode, continue treatment for 6-12 months after remission to prevent relapse. For recurrent or severe episodes, long-term maintenance may be necessary.

Clinical Pearls & FAQs

  • Anxiety Spike: Warn patients that anxiety may briefly worsen when starting an antidepressant. This prevents early discontinuation.
  • Sexual Side Effects: Patients rarely volunteer this information, but it is a common reason why patients stop the medication without telling their provider. Ask directly. If present, consider switching to Bupropion or adding it as an adjunct.
  • Pharmacogenomics: Tests like GeneSight are not a “magic bullet” for initial selection. They help guide dosing based on metabolism but do not predict efficacy. Reserve them for treatment-resistant cases or those with unusual side effects. Most insurances will not pay for gene-drug interaction tests unless the patient has failed at least two antidepressant trials.
  • Exercise as Medicine: For mild-moderate depression, exercise can be as effective as medication. Use behavioral activation (“Just walk to the mailbox today”) to help patients overcome the inertia of depression.
  • Cannabis Use: Daily cannabis use can mimic or worsen depression. While we can’t force patients to quit, encouraging a “tincture of time” off the substance can clarify the diagnosis. Note that substance-induced depression often resolves without antidepressants once substance use stops.

When to Refer to Psychiatry (if/when available) or call the UW Psychiatry Consultation Line (PCL)

Primary care is the ideal setting for uncomplicated depression. Consider referral if:

  1. Diagnosis is unclear (e.g., suspected bipolar or schizoaffective disorder).
  2. Treatment resistance (failed 2+ medication trials).
  3. High safety risk (active suicidal ideation, psychosis).
  4. Complex comorbidities (severe substance use, personality disorders).

If a referral to psychiatry is not possible, you can always call the PCL for free clinical advice about your adult patients with mental health and/or substance use conditions. Prescribing providers can call any time, 24/7, and non-prescribing providers can call Mon-Fri, 8 a.m. – 5 p.m. (excluding holidays). 877-WA-PSYCH/877-927-7924 We are here to help!

To see Dr. Duncan’s complete UW PACC presentation on this topic, click on this link: Initial Treatment of MDD

Mark Duncan, MD

Dr. Duncan, trained in both family medicine and addiction psychiatry, practices at the intersection of mental health and primary care. He is the co-medical director for the University of Washington Psychiatry and Addiction Case Conference (UW PACC), a weekly online learning collaborative to help community providers across the state improve their psychiatric and addiction clinical skills. Dr. Duncan is one of the PCL’s core weekday faculty where his unique expertise in primary care and psychiatry is available to healthcare providers across Washington.

PCL intake process changes starting January 2026

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Effective January 20, 2026, the PCL no longer asks for patient names or dates of birth. This change will enhance patient privacy and streamline the intake experience.

Action Required for Repeat Patient Consultations: Because we will no longer use name or date of birth identifiers to track patients, we are moving to a PCL Record Number system to help maintain continuity of care.

  • Look for the number: Every PCL consultation note we send you will include a unique PCL Record Number.
  • Have it Handy: If you call back regarding the same patient, please try to have the PCL Record Number or the previous consultation note available. This will help us more quickly locate and reference previous recommendations.

If you have any questions or concerns, please don’t hesitate to contact us at pclwa@uw.edu. 

Thank you for your partnership in prioritizing patient privacy while helping us maintain the quality of our consultation services.

Supporting Patients with Substance Use Disorders

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Substance use disorders (SUD) are common but underdiagnosed. According to the 2022 National Survey on Drug Use and Health, approximately 48.7 million Americans aged 12 or older had a SUD in the past year, yet only about 6% received treatment. That same report found that approximately 21.5 million adults in the US have co-occurring mental health and substance use disorders.1 The good news is that all health care providers can help improve care for patients with SUDs by effectively screening and incorporating treatment for these conditions into their practice. Engaging patients early in the disease process can reduce morbidity, mortality, and healthcare costs and is most effective when providers use a compassionate, nonjudgmental style.

SCREENING MATTERS

The U.S. Preventive Services Task Force (USPSTF) recommends that all adults be screened for unhealthy substance use.2 Screening should be universal and not based solely on clinical suspicion, which can be biased and miss patients who need our help. A variety of tools with validation can be administered prior to the encounter with the provider, allowing for further discussion if the screen was positive. The following screeners, except the DAST, are publicly available, free to use and can be found on the PCL website Resources page.

Alcohol Use Disorders Identification Test (AUDIT)

  • AUDIT-C: A brief, validated 3-question screen that identifies hazardous drinking patterns that may be impacting physical health (e.g., hypertension, liver function) and to create an opening for brief intervention and counseling. It can be helpful for fast, universal screening during annual check-ups or new patient visits.

  • AUDIT: If the AUDIT-C is positive, the full 10-item questionnaire is a good follow-up to gather more information on levels of consumption, signs of dependence, and alcohol-related problems. Because alcohol use can mimic or worsen psychiatric symptoms like depression, anxiety, and insomnia, use of the AUDIT can help clinicians differentiate symptoms, inform diagnosis, and aid in treatment planning. It is also highly regarded for its reliability and validity across diverse populations.

Drug Abuse Screening Test (DAST)

  • DAST-10: A 10-question screen that assesses the degree of problems related to drug use. The DAST is a “yes/no,” self-report questionnaire that can be administered by a healthcare professional or completed by patients. It only takes 5 to 10 minutes to complete and screens for problems related to the use of illicit drugs, as well as the misuse of prescription or over-the-counter drugs. 

The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST)

  • ASSIST: A more detailed tool with 2 to 8 questions (more depending on how many substances the patient is using) that screens for nicotine, alcohol and other commonly abused substances. It is used when a patient has screened positive on a briefer tool or when you suspect polysubstance use. The ASSIST should be completed with the patient and provider together to review the tool generated substance-specific risk score and built in patient education. It also helps clinicians consider the best level of intervention: brief advice in-clinic or referral to a specialist for higher-risk use.

FROM SCREENING TO ENGAGEMENT

If a patient does screen positive, the style in which the patient is engaged in discussion about diagnosis and treatment is critical to engaging patients successfully in care. Motivational interviewing (MI) is a patient-centered communication style that enhances engagement by expressing empathy, supporting self-efficacy, and avoiding confrontation. MI can help you engage with patients who are not yet expressing interest in change or are contemplating it.

Key MI techniques include using (OARS):

  • Open-ended questions – invite more than a “yes” or “no” answer and encourage elaboration. “Can you tell me what you enjoy about using alcohol?” “Can you tell me more about why you are worried about your alcohol use?”

  • Affirmations – Recognize and acknowledge your patient’s strengths, efforts, and intentions. “You are understandably concerned about how alcohol is impacting your health.”

  • Reflective listening – Demonstrate that you have heard and understood your patient’s perspective. “You’re worried that stopping might affect your ability to cope with stress.”

  • Summarizing – Periodically gather together what your patient has said, showing that you are listening carefully and helping them integrate their thoughts. “You are interested in reducing your drinking but total abstinence from alcohol is not your goal.”

MI techniques can be highly effective in helping the patient resolve their own ambivalence about their use while increasing motivation to change behavior. It also helps patients feel heard and not judged which is important for ongoing engagement in care. Further, MI improves both patient satisfaction and outcomes while improving provider well-being through better patient-provider relationships, more effective interactions, and reduced stress.3

TREATMENT CAN START IN PRIMARY CARE

Treatment of SUD in primary care settings is effective, even when severe disorders are present. For instance, primary care-based buprenorphine treatment has previously been shown to be effective in treatment patients with OUD with similar outcomes in terms of treatment engagement to subspecialty care.4 All health care providers can help reduce the burden of substance use disorders. Universal screening, empathetic communication, and medical treatment can save lives and transform the trajectory of patients struggling with substance use.

YOU’RE NOT ALONE – THE PCL IS HERE TO HELP

Supporting patients with substance use or co-occurring disorders is a team effort. If you have questions about how to screen, engage, or treat your adult patients with these or any other behavioral health conditions, please call the PCL. We are here to help!

Prescribing providers may call any time, 24/7, and non-prescribing providers may call Mon-Fri, 8 a.m. – 5 p.m. (excluding holidays) at 877-927-7924 (877-WA-PSYCH) or schedule ahead at a time that is best for you.

AUTHOR

Jonathan Buchholz, MD

Dr. Jonathan Buchholz is an Addiction Psychiatrist at the Veteran’s Administration, Puget Sound, and is the Director of the UW Department of Psychiatry and Behavioral Sciences Addictions Psychiatry Fellowship program. He is also the lead MD for the PCL’s Medication for Opiate Use Disorder expansion.

References:

  1. SAMHSA. 2022 National Survey on Drug Use and Health (NSDUH).
  2. U.S. Preventive Services Task Force. Screening for Unhealthy Drug Use. JAMA. 2020;323(22):2301–2309.
  3. Pollak, K. I., et al. (2016). Effect of teaching motivational interviewing via communication coaching on clinician and patient satisfaction in primary care and pediatric obesity-focused offices. Patient education and counseling, 99(2), 300-303.
  4. Xu KY, Gertner AK, Greenfield SF, Williams AR, Grucza RA.  Treatment setting and buprenorphine discontinuation: an analysis of multi-state insurance claims.  Addict Sci Clin Pract. 2024;19(1):17.

RELATED RESOURCES

UW Psychiatry and Addictions Case Conference (PACC)*

Should I Use Benzodiazepines for Ambulatory Alcohol Withdrawal Management? by Lucy Liu, MD

Helping Patients Get to and Utilize Twelve-Step Programs by Richard Ries, MD

Discussing Cannabis Use with Clients or Patients by Jason Kilmer, PhD

UW Addictions, Drug and Alcohol Institute (ADAI)

Retention Toolkit: Motivational Interviewing Trainings and other information on MI

Substance Use Resources in Washington State for Professionals/Providers A curated selection of resources and information for professionals and providers in the substance use disorder field.

Non-stimulant Treatment Options for Adult Attention Deficit Hyperactivity Disorder (ADHD)

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The estimated prevalence of adult ADHD in the United States is often cited at 4.4%, referencing a 2021 report on the results of the National Comorbidity Survey [1]. Many studies have documented the impact of untreated adult ADHD on morbidity and mortality. Adult ADHD is also associated with an increased risk for anxiety disorders, bipolar disorder, major depression, substance use disorders, and intermittent explosive disorder.

Our PCL program has received numerous calls regarding the treatment of adult ADHD. Frequently, the questions surround the use of non-stimulant medications. Additionally, there are patients who would prefer to try non-pharmacologic interventions before considering augmentation with a medication. 

Cognitive Behavioral Therapy (CBT) has shown efficacy for adult ADHD in multiple research trials. CBT has not only been shown to be effective for core ADHD symptoms, but several adult studies have also noted a benefit for CBT in certain quality of life measures. Many participants note that CBT can be a game changer for procrastination, for example. CBT for ADHD also helps patients challenge their negative self-beliefs, which can improve co-morbid mood and anxiety symptoms.

Atomoxetine is a norepinephrine reuptake inhibitor that is FDA-approved for adult ADHD. This medication is not a stimulant and has almost no abuse potential. Both atomoxetine and stimulants are more effective than placebo for adult ADHD.  Most algorithms refer to atomoxetine as a 2nd-line medication intervention (with stimulants being 1st-line). However, there are no blinded, head-to-head trials comparing these two classes. 

Atomoxetine is metabolized by cytochrome p450 2D6 and thus there are potential drug interactions. It also has a Black Box Warning for suicidality in certain patient populations. Atomoxetine can trigger mania or hypomania, which is especially notable given the higher rate of bipolar disorder in adults with ADHD. For a complete list of atomoxetine’s potential side effects, please refer to medication reference material (MicroMedex, etc.).

If you would like more information on treatment options for adult ADHD, please call the Psychiatry Consultation Line (877-WA-PSYCH/877-927-7924) and one of our psychiatrists would be happy to review the data with you and how it applies to your patient. Similarly, if you have questions regarding treatment of ADHD in perinatal patients, please contact our Perinatal Psychiatry Consultation Line at 877-725-4666.

[1] Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006 Apr;163(4):716-23. doi: 10.1176/ajp.2006.163.4.716. PMID: 16585449; PMCID: PMC2859678.

Author

Ryan Kimmel, MD

Dr. Kimmel is the Chief of Psychiatry at both UWMC campuses, Montlake and Northwest, and Director of Psychiatric Consultation and Telepsychiatry Programs, including the Psychiatry Consultation Line. His clinical focus is on working with patients who are hospitalized with simultaneous psychiatric and medical issues. Academically, Dr. Kimmel most often teaches psychiatry trainees about psychopharmacology for refractory mood, anxiety, and psychotic disorders.

Related Resources

UW Psychiatry and Addictions Case Conference (PACC)

Cognitive Behavioral Strategies for ADHD, presented by Katherine Walukevich-Dienst, PhD

ADHD Update: Clinical and Diagnostic Issues, presented by Mark Stein, PhD, ABPP

Treating ADHD in the Setting of Bipolar Disorder, presented by Kimiko “Koko” Urata, MD

The UW PACC is a free, weekly teleconference connecting community providers from across Washington with UW Medicine psychiatrists, psychologists, and addictions experts. Sessions include both an educational presentation and (de-identified) clinical case presentations allowing providers an opportunity to receive feedback and recommendations from interdisciplinary attendees. CME is available for free or for a small fee. Visit the PACC website for more information.

PCL Satisfaction Survey Feedback, 2023-2024

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Every summer, we ask community providers who’ve consulted the PCL over the past year to share with us their feedback and improvement ideas. In 2024, we received survey responses from providers in 25 of the 35 Washington counties who consulted the PCL during this time. THANK YOU ALL for your time and thoughtful feedback.

Of those who responded to the survey,

  • 98% were satisfied or very satisfied with the information and recommendations they received
  • 99% were satisfied or very satisfied with the time it took to connect to the PCL psychiatrist
  • More than 91% indicated the consultation helped them care for a specific patient
  • 89% said it would help in the care of future patients
  • 95% of respondents said they would use the PCL again and would recommend the service to others

PCL Improvement Ideas

Can the PCL have psychiatrists available on evenings and weekends?

  • Good news! The PCL is available 24 hours/day, 7 days/week to prescribing providers so call us anytime you need a consultation.

It would be great if the PCL psychiatrists could help with legal questions.

  • PCL psychiatrists are clinical consultants, and legal advice is specifically outside the scope of the program, unfortunately.

Can the PCL psychiatrists come to our county and offer trainings?

  • If we had the bandwidth to do this statewide, we would! Instead, we share educational resources on our website and in every PCL newsletter, please visit PCL News for previous editions.