Category: medications

Treatment of Adults with Opioid Use Disorder

Posted on

Do you have patients who are misusing opiates? Do you wonder if you can manage prescribing medications for opioid use disorder (MOUD) or have questions about what to prescribe? Drug overdose deaths in the United States are at an all-time high, with most caused by opioid use, namely fentanyl. The good news is that effective medication treatments for opioid use are available, and in case you didn’t know, Washington providers can call the Psychiatry Consultation Line at 877-927-7924 to consult with our psychiatrists about using these treatments with your adult patients.

It’s critical for more clinicians to explore whether they can prescribe MOUD; in 2019, only 18% of people with opioid use disorder (OUD) received MOUD in the prior year. What are the MOUD options for your patients living with OUD?

Methadone 

The three FDA-approved MOUD options are methadone, buprenorphine and naltrexone. Methadone is a full mu-opioid agonist that has been exhaustively studied and shown to be safe and effective for patients with OUD, particularly when dosed above 60 mg per day. Because of the time involved in titration, achieving a dose of methadone that alleviates cravings and protects patients from overdose can take weeks. Despite the efficacy data, methadone is the most tightly regulated MOUD, and it is only accessible through DEA-approved treatment facilities. Many counties in Washington have no methadone clinics, leaving those with OUD only two MOUD options: naltrexone and buprenorphine.

Naltrexone

Naltrexone, particularly in the form of the 380 mg per month, long-acting injectable is another option for patients. As a full mu opioid blocker, initiation of naltrexone requires full withdrawal from opioids. Starting naltrexone prior to completion of opioid withdrawal can result in precipitated withdrawal. Many patients are unable to achieve full cessation and thus studies have shown higher dropout rates with naltrexone for OUD compared to buprenorphine.

Buprenorphine

Buprenorphine is the third FDA-approved MOUD with evidence similar to methadone in terms of treatment outcomes. In years past, prescribing buprenorphine required at least 8 hours of training and an x-waiver. As of January 2023, this requirement was dropped and anyone with a standard DEA registration number can prescribe buprenorphine. Unlike methadone, buprenorphine can be prescribed in an office-based setting, making it more accessible for patients.

As a partial agonist with a high binding affinity for the mu-opioid receptor, buprenorphine is a very safe option for OUD. Even at maximum doses, patients do not experience respiratory depression with the medication alone. Further, doses of buprenorphine, which protect patients from overdose, can be achieved quickly in one or two days. Given the pharmacologic properties of buprenorphine, patients must be in some degree of opioid withdrawal prior to initiating buprenorphine, as it can otherwise precipitate opioid withdrawal. Typically, it is recommended for patients to achieve a clinical opioid withdrawal scale (COWS) score of 8 or more prior to initiating buprenorphine. Though precipitated withdrawal is not necessarily dangerous, patients feel extremely uncomfortable and can have negative connotations with buprenorphine, reducing their likelihood of continuing the medication in the future.

Thankfully this outcome is a relatively rare occurrence. In one recent study less than 1% of patients experienced precipitated withdrawal when dosed with buprenorphine after achieving a COWS score greater than 8. Techniques for initiating buprenorphine varies significantly, ranging from “low dose induction,” the practice of giving small doses of buprenorphine with gradual increases over time to “standard induction,” giving 4 mg -12 mg of buprenorphine in the first day, to “high dose inductions” initiating higher doses of buprenorphine, 16 mg to 32 mg quickly following emergence of withdrawal symptoms.

Buprenorphine Treatment Guidelines

Regardless of the initiating dose, the goal of treatment is to achieve a dose of buprenorphine that eliminates opioid withdrawal, significantly reduces or eliminates craving to use opioids, and blocks the effects of illicit opioids to the degree that the patient has significantly reduced, or better yet, stopped use of illicit opioids all together. If patients have cravings to use, evidence of withdrawal from opioids, or continue using illicit opioids, increasing the dose of buprenorphine should be considered. The current maximum dose is 32mg daily.

Previous guidelines have suggested that doses of buprenorphine beyond 24 mg may not be necessary, but these recommendations were based primarily on data associated with patients using heroin. In the current era where the illicit opioid market is dominated by fentanyl, patients may well require higher doses of buprenorphine. Typically, buprenorphine has been dosed once daily, but for some, 2-4 doses spread throughout the day are preferred. Buprenorphine has multiple formulations for the treatment of OUD which include sublingual, buccal, implantable, and long-acting subcutaneous injectable versions.

There are no clear data on the length of time patients with OUD should remain on MOUD. However, after cessation of medications, rates of return to use of opioids is high, so most experts recommend ongoing maintenance therapy with buprenorphine or methadone. For more information on treatment of patients with MOUD, please see the resources below. And please call the PCL at 877-927-7924 if you are a Washington provider who would like to consult about your adult patients with mental health and/or substance use care needs.

Author

Jonathan Buchholz, MD
Director, Addictions Psychiatry Fellowship; Medical Director of Inpatient Psychiatry, VA Puget Sound

Dr. Buchholz specializes in working with individuals experiencing co-occurring mental health and substance use disorders, a process that reminds him of he amazing resiliency that lies within us all.

Related Resources

Practice-Based Guidelines: Buprenorphine in the Age of Fentanyl
Provides practical clinical practice-based guidance, based on available research combined with emerging clinical experience, on the use of buprenorphine in the treatment of individuals using fentanyl and other highly potent synthetic opioids.

Linking People with Opioid Use Disorder to Medication Treatment
This prevention resource presents strategies that can help
state, local, and tribal leaders and healthcare professionals link
persons living with OUD to evidence-based care. Strategies are
based on the best available evidence.

Medications for Opioid Use Disorder
The Executive Summary of this Treatment Improvement Protocol provides an overview on the use of the three Food and Drug Administration-approved medications used to treat opioid use disorder—methadone, naltrexone, and buprenorphine—and the other strategies and services
needed to support recovery.

Providers Clinical Support System-Medications for Opioid Use Disorders
A program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA) and created in response to the opioid overdose epidemic. PCSS-MOUD’s goal is to provide evidence-based practices to improve healthcare and outcomes in the prevention of those at risk and treatment for individuals with an opioid use disorder (OUD).

10 Tips for Prescribing in the Perinatal Period

Posted on
Perinatal person with baby

Psychiatric disorders are common during pregnancy and postpartum. For example, rates of perinatal depression and anxiety are 15-20%. Twenty percent of people with postpartum depression have a bipolar spectrum disorder. In addition, many people have pre-existing psychiatric conditions and are already taking psychotropic medications when they become, or are planning to become, pregnant. The overall goal of treatment during pregnancy is to use the lowest number and dosages of medications possible, while effectively treating the underlying psychiatric disorder(s).

Although the Perinatal PCL receives questions about diagnoses, non-medication treatments, and resources and referrals, many calls are about prescribing and the effects of medications during pregnancy and lactation. Here, we provide some general guidelines about prescribing during the perinatal period and some resources to find information about risks of specific medications.

What are some general guidelines about prescribing during the perinatal period?

1. Consider risks during pregnancy whenever prescribing medication for someone of childbearing potential.
About 50% of pregnancies are unplanned. Considering, and informing people of childbearing potential about, risks of their medication(s) during pregnancy helps to maximize prescribing of safer medications and avoid patients’ suddenly discontinuing needed medication if they find out they are pregnant.

2. Make any medication changes before pregnancy if possible.
This minimizes the number of exposures for the baby and maximizes stability for the parent. Changing a newer medication with less data regarding safety in pregnancy to an older medication with more safety data can be done before pregnancy, if desired. Making this change once the patient is already pregnant involves exposing the baby to two medications instead of one and potentially causing worsening of the parent’s psychiatric condition during pregnancy.

3. Ideally, the patient should be psychiatrically stable for at least 3 months before trying to conceive.
Although this is not always possible, it decreases the risk of relapse and exposure of the baby to risks of untreated/undertreated psychiatric illness.

4. Avoid polypharmacy whenever possible.
Prescribing the fewest medications possible to effectively treat the patient’s psychiatric disorder reduces exposures for the baby. Reviewing the need for each medication is especially important when someone is taking multiple medications and/or more than one medication in a class (e.g., two or more antidepressants, two or more antipsychotics, multiple antianxiety/hypnotic medications, etc.).

5. Avoid Depakote.
Depakote (valproic acid) is a commonly prescribed mood stabilizer for patients with bipolar disorder. Depakote is a known teratogen (rate of malformations elevated in all dosage ranges and 25% at doses above 1450 mg/day) and is associated with significantly decreased IQ in children exposed in utero.

6. Optimize non-medication treatments.
At all times, and especially during the perinatal period, we want to maximize the use of evidence-based non-medication treatments such as psychotherapy. Even if someone requires medication for effective treatment of their condition, non-medication treatments can help minimize numbers and dosages of medications and increase effectiveness of treatment.

7. Remember that an untreated/undertreated psychiatric disorder also poses risks to the parent and the baby.
Untreated/undertreated psychiatric disorders pose significant risks for parents and babies. For example, perinatal depression is associated with higher rates of preterm birth, low birth weight, problems with attachment and bonding, and increased rates of psychiatric disorders in childhood and adolescence. For this reason, it is important to treat psychiatric disorders effectively during the perinatal period.

8. If you are thinking of stopping your patient’s psychotropic medications because they are pregnant, please call us first.
Discontinuing medications abruptly can precipitate relapse (another exposure for the baby and risk for the parent). Also, stopping some medications can cause withdrawal symptoms that are potentially dangerous (e.g., benzodiazepines) or unpleasant (e.g., antidepressants). We would be happy to help you sort out which medications to discontinue and safe tapering schedules.

9. Prescribing during the perinatal period requires a risk-risk discussion.
Informed consent during the perinatal period involves collaborating with the patient in discussing and weighing risks of medication for the fetus/baby, risks of the psychiatric disorder, and possible alternative treatments.      

10. Use a patient-centered and team approach.
In addition to collaborative decision-making with, and support of, the patient, this includes involving family members and communicating with other care providers. It is important to educate the partner and/or family members about the risks and benefits of treatment as well as warning symptoms of relapse. Communication with obstetric and pediatric providers minimizes the patient’s hearing conflicting opinions and being confused and concerned.   

The Perinatal PCL is a free, state-funded, provider-to-provider consultation line like the Psychiatry Consultation Line (PCL) but focused on behavioral health disorders and symptoms during the perinatal period (pregnancy and the first 12 months postpartum). We are available at 877-725-4666 or by email at ppcl@uw.edu, weekdays 9-5. Like PCL, we also offer scheduled consultations.

Any healthcare provider in Washington State can call us with any behavioral health-related questions about a patient/client who is pregnant, planning pregnancy, postpartum, or who has pregnancy-related complications (e.g., infertility, pregnancy loss). Perinatal PCL is staffed by University of Washington perinatal psychiatrists, an addiction psychiatrist with expertise in the perinatal period, and our program coordinator, who is trained in social work. We offer psychiatric consultation and local perinatal mental health resources. For more information about Perinatal PCL, and to access our online Perinatal Mental Health Care Guide, please visit our website.

Author

Deb Cowley, MD
Board-certified psychiatrist at UWMC-Roosevelt
UW professor of Psychiatry and Behavioral Sciences
Medical director, Perinatal PCL

Dr. Cowley has expertise evaluating and treating women who have mental health issues during pregnancy and postpartum, and throughout their life cycle, including premenstrual and menopause-related psychiatric symptoms. Her clinical interests include anxiety disorders, depressive disorders, obsessive compulsive and related disorders, panic disorder, postpartum depression, evidence-based medicine, maternal mental health and women’s health.

Related Resource

Management of Psychotropic Drugs During Pregnancy
Psychiatric conditions (including substance misuse disorders) are serious, potentially life threatening illnesses that can be successfully treated by psychotropic drugs, even during pregnancy. This review presents an up to date and careful examination of the most rigorous scientific studies on the effects of psychotropic drugs in pregnancy.

Other Resources

InfantRisk for Healthcare Providers
This collection of apps is for healthcare providers and parents about the safety of medications during pregnancy and breastfeeding. 

LactMed
This database of drugs and other chemicals provides information about the safety of exposure during breastfeeding.

Reprotox
This database of medications highlights their effects during pregnancy, breastfeeding, and development. (Requires subscription.)

MotherToBaby
These fact sheets are for parents regarding risks of drugs (including non-prescribed drugs) during pregnancy and breastfeeding. 

Perinatal Support Washington
This non-profit organization provides a warm line, support groups, peer support, resources, and therapy referrals to support emotional wellbeing for new parents. 

Treatment of Adult Patients with Obsessive-Compulsive Disorder

Posted on
Image for OCD treatment

The lifetime prevalence of obsessive-compulsive disorder (OCD) amongst adults in the United States is 2-3%. While most providers can list the most common symptoms of OCD, the diagnosis is rare enough that it may have been a while since you got an update on useful screening tools and treatment recommendations. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is a good place to start, and you can find this document on the Resources section of our website. The Y-BOCS contains a list of symptoms that can be helpful for making the diagnosis, as well as a rating scale that can be used to track treatment efficacy.

There are a wide range of obsessions and compulsions that can be seen in OCD and thus the symptom checklist on the third page of the Y-BOCS document can be very helpful when trying to establish the diagnosis. Moreover, the rating scale on the first two pages not only helps with establishing the diagnosis but is also useful for tracking the improvement seen with treatment.

The first-line treatment for adults with OCD is cognitive behavioral therapy (CBT) with exposure and response prevention. When medication is added to CBT, the usual first choice is an SSRI. Though an 8-week trial of an SSRI is adequate for some behavioral health diagnoses, patients with OCD may see better results from SSRIs at 16 weeks. Moreover, some patients with OCD require SSRI dosing that is titrated up toward the higher end of the usual dosage spectrum. This might mean, for example, a final daily sertraline dose of 150-200mg, rather than 50-100mg, if the patient can tolerate the higher dose. 

For patients who have not responded to one or two different SSRI trials, clomipramine is sometimes trialed. SSRIs and clomipramine are not used together since the combination increases the risk of serotonin syndrome. In terms of efficacy, some clomipramine studies suggest this medication is superior to SSRIs in OCD. However, clomipramine is a tricyclic antidepressant and thus has more side effects than SSRIs, with anticholinergic side effects especially intolerable for some patients. Tricyclics also have a higher risk of cardiac side effects, even at normal doses, and are more lethal on overdose than SSRIs.

Atypical antipsychotics have some data as an augmentation strategy for patients who have a partial response to SSRIs or clomipramine. Lamotrigine and topiramate have a small amount of data for augmentation in refractory cases, as well. Clonazepam and lorazepam, on the other hand, do not generally demonstrate efficacy in studies of augmentation or monotherapy for OCD.

If you are considering using a medication for OCD, please first review your own reference material for full details on indications, side effects, dosing, monitoring requirements, and drug interactions. For reference, we most often use Micromedex, UpToDate, or Epocrates. Additionally, there are free databases available to Washington providers at heal-wa.org/professions.

If you would like more information on the spectrum of medications for OCD, 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.

Author

Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line


Learn More

OCD: Diagnosis and Treatment
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Deborah Cowley, MD
The objectives of this presentation are to: 1) review the diagnosis of OCD and related disorders; 2) discuss the epidemiology, differential diagnosis, and comorbidity; and 3) discuss treatment of OCD and related disorders. 

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Antipsychotic-associated Metabolic Syndrome

Posted on
Colorful image to show range

When providers reach out to the PCL program with questions about antipsychotics, we often include a document that outlines a schedule for monitoring metabolic side effects in our write-ups. While we follow this monitoring schedule for all antipsychotics, there are certain second-generation antipsychotics that are more notorious than others.

Olanzapine and clozapine, for example, are associated with the most weight gain. On the other end of the spectrum, ziprasidone and aripiprazole are associated with the least. Beyond the long-term cardiovascular risks, tracking the metabolic syndrome is also important because patients are understandably reluctant to continue taking medications that cause weight gain. 

While there have been studies to suggest that metformin may have a modest, short-term benefit for olanzapine-associated weight gain, there is also data that switching from olanzapine to aripiprazole or ziprasidone can result in the loss of some of the weight gained while on olanzapine. There is a risk of decompensation when switching from one antipsychotic to another and the decision to switch is thus ultimately based on a variety of patient-specific factors. There are not yet any published, placebo-controlled trials on the use of semaglutide or tirzepatide for antipsychotic-associated weight gain.

Antipsychotics can also cause glucose dysregulation and lipid disturbance. These abnormalities can arise even in patients who are not gaining weight, which is why we monitor fasting labs as a matter of course. For a useful way to visualize the spectrum of antipsychotics in terms of their metabolic side effects, I’d recommend looking at Figure 3 of Pillinger’s article on antipsycohtics in Lancet Psychiatry 2020; 7: 64-77. In this “heat map,” red are the worst offenders and yellow the least, though you can see that no antipsychotic is wholly innocent.

If you would like more information on the spectrum of antipsychotic side effects, please call the Psychiatry Consultation Line (877-WA-PSYCH) and one of our psychiatrists would be happy to review the data with you.

Author

Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line

New Generic Option for Treating Bipolar

Posted on


Within the last few months, a generic formulation of Latuda (lurasidone) has become available. Should you consider prescribing it for adult Bipolar I Depression?

Previously, this medication cost >$1,200/month and was thus out of reach for most patients and/or required insurance pre-authorization. Now that the price of lurasidone has fallen dramatically, it is worth comparing this medication to quetiapine, which is also generic and also has an FDA indication for adult Bipolar I Depression.

There aren’t very many head-to-head trials, but in meta-analyses of monotherapy for adult Bipolar I Depression, both lurasidone and quetiapine appear to be efficacious. Several published treatment algorithms consider both medications to be first-line options as monotherapy for this indication. In other studies, lurasidone has demonstrated efficacy for adult Bipolar I Depression when used as an adjunct to lithium or divalproex and, indeed, Latuda garnered FDA-approval for adjunct use for this indication.

FDA package inserts are available on the FDA approved drugs site. Package inserts contain a lot of useful information and are likely underutilized in our era of quick, app-based, medication references. When comparing the data reported in the package inserts for lurasidone and quetiapine, lurasidone appears to have a lower incidence of the antipsychotic-associated metabolic syndrome (weight gain, new-onset diabetes, new-onset hyperlipidemia, etc.). Lurasidone, at least at low doses, is also felt to be less sedating than quetiapine. However, when compared to quetiapine, lurasidone appears to have a higher incidence of parkinsonism, akathisia, and other D2 blockade-mediated side effects. For more details on the side effects of these medications, including information on the Black Box warnings, QTc prolongation, monitoring of the metabolic syndrome, and other adverse effects, please refer to your own medication reference material or the free sites available via Heal WA.

Another important difference between lurasidone and quetiapine is that lurasidone needs to be taken with a >350 calorie meal. This dramatically increases the absorption of lurasidone. However, food insecurity is a problem experienced by many people in our society, and it is important to ask your patients if they have regular access to a >350 calorie dinner.

Lurasidone dosing is usually initiated at 20mg/day. Though the FDA max dose is 120mg/day, some studies of adult Bipolar I Depression suggest that high-end dosing does not necessarily increase efficacy but might increase the risk of side effects. The mean (SD) lurasidone dose was 64.1 (14.4) mg in a 24-week open label study authored by Ketter et al for the journal Depression and Anxiety. Thus, rather than automatically pushing the lurasidone dose to the top end, it could be useful to first give the patient a good trial in the middle of the dosing range.

If you would like more information on the treatment of adult Bipolar I Depression, please call the Psychiatry Consultation Line (877-WA-PSYCH) and one of our psychiatrists would be happy to review the options with you.

Author

Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line


Learn More

Bipolar Disorder — Screening and Diagnosing in Primary Care
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Joseph Cerimele, MD, MPH
The objectives of this presentation are to describe1) the clinical epidemiology of individuals with bipolar disorder in primary care settings; 2) techniques to improve the recognition of bipolar disorder in primary care patients; and 3) clinical characteristics of patients with bipolar disorder in primary care. 

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Lack of Evidence: Gabapentin in Bipolar Disorder

Posted on

When it comes to treating adults with bipolar disorder, gabapentin appears to be everything you’d want in a medication…except for efficacy.

Prescribers wish that gabapentin had utility in bipolar disorder because gabapentin isn’t a P450 substrate, is renally excreted, and is generic and thus relatively affordable. Unfortunately, gabapentin does not demonstrate efficacy in randomized trials for bipolar disorder and current treatment guidelines do not emphasize its use. Despite of the lack of evidence, reviews of gabapentin prescribing patterns in the United States show that this medication is still being used with alarming frequency for bipolar disorder.

There are now five medications with specific, FDA approval for acute bipolar depression. Moreover, there are at least a dozen medications with FDA approval for acute mania. Many of these options are available in generic formulations.

Instead of reaching for gabapentin as a potential intervention for bipolar disorder, please call the Psychiatry Consultation Line (877-WA-PSYCH) and one of our psychiatrists would be happy to review treatment options that have better evidence.

You can also call the PCL for advice regarding differential diagnosis, non-pharmacologic interventions, and treatment monitoring. In complicated clinical scenarios, discussing a patient’s care with a colleague can help you formulate a more comprehensive treatment plan.  

The PCL is a free resource for healthcare providers in Washington State to consult with a psychiatrist about their adult patients with mental health or substance use conditions. Learn more at pcl.psychiatry.uw.edu.

If you are considering using a medication for bipolar disorder, please first review your own reference material for full details on indications, side effects, dosing, monitoring requirements, and drug interactions. For reference, we most often use Micromedex, UpToDate, or Epocrates. Additionally, there are free databases available to Washington providers at heal-wa.org/professions.


Author

Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line


Learn More

Managing Bipolar Depression in Primary Care
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: John S. Kern, MD
The objectives of this presentation are to 1) recognize the predominant role of depressive episodes in the morbidity associated with bipolar disorder; 2) summarize the outcomes of the SPIRIT study; and 3) apply an orderly approach to the care of bipolar depression.

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Mirtazapine in major depressive disorder in adults

Posted on
500500

Mirtazapine garnered FDA approval as an antidepressant in 1997. It has been generic for so long that it no longer has an advertising budget and thus you won’t see commercials for it on late-night television. Mirtazapine impacts serotonin and norepinephrine systems in the brain but is not a reuptake inhibitor. While SSRIs are generally considered first-line in major depressive disorder, mirtazapine is a medication worth remembering in certain situations. 

Mirtazapine does not inhibit P450 enzymes and thus can be useful in depressed patients who have complex medical histories and are on complicated (and ever changing) medication regimens. 

Mirtazapine does not cause sexual dysfunction greater than placebo, making it a potentially useful alternative for patients with depression and intractable, SSRI-associated, sexual dysfunction. Sexual side effects are seen in as many as 50% of patients on SSRIs and are frequently cited by patients as a reason for medication discontinuation.

Per the original package insert, 17% percent of patients taking mirtazapine experienced appetite stimulation. “Weight gain” is often all that prescribers remember about mirtazapine. It is true that this medication has a higher risk of weight gain than SSRIs, that this issue needs to be discussed with patients, and that weight needs to be closely monitored. However, it is also notable that only a minority of patients have this side effect. On the other hand, for patients who experience a profound loss of appetite as a feature of their depression, the potential for appetite stimulation with mirtazapine might be seen as an advantage. 

Mirtazapine is a strong antihistamine and, indeed, the original package insert notes that 54% of patients on mirtazapine reported sedation, compared to only 18% for placebo. This side effect can represent a hindrance or a benefit, depending on the specific features of the patient’s depression and on the degree of sedation. For example, psychiatrists sometimes use mirtazapine as an augmentation strategy for patients who have had a partial response to SSRIs and whose depressive symptoms include prominent initial insomnia. It should be noted that oversedation can impair performance and thus this side effect needs to be monitored by the patient and the prescriber.

Unlike the SSRIs and SNRIs, mirtazapine’s only FDA indication is for major depression. In the intervening 25 years since its FDA approval, the bulk of mirtazapine’s positive data remains for its use in major depression. There is some mixed data (variable strength of study and variable results) in generalized anxiety disorder and social anxiety disorder. However, we do not usually consider mirtazapine as a first- or second-line agent for monotherapy in anxiety disorders.

If you are considering using mirtazapine, please refer to your own reference material for full prescribing information regarding medication dosing, risks, benefits, side effects, monitoring requirements, and drug interactions.  We most often use Micromedex, UpToDate, or Epocrates.  Additionally, there are free databases available to Washington State providers at https://heal-wa.org/professions/. You can also call the Psychiatry Consultation Line (877-927-7924) for clinical advice on using mirtazapine in the treatment of major depressive disorder in adults as well as assessment, treatment decisions and monitoring of mental health conditions in general. Even in complicated clinical scenarios, discussing a patient’s care with a colleague can lead to a path forward.

Author
Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line

Learn More
Treatment Resistant Depression
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Mark Duncan, MD
The objectives of this presentation are to 1) discuss pros and cons of treatment guidelines, 2) walk through cases to determine best options, and 3) Improve confidence in decision making around treatment resistant depression.

Using Stimulants to Augment Depression Treatment
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Ramanpreet Toor, MD
The objectives of this presentation are to review evidence of psychostimulant use in the treatment of depression.

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Non-stimulants for adult ADHD

Posted on

While the data on the efficacy of stimulants in adult ADHD is robust, we have had numerous calls to the PCL program from providers seeking information on medications that have a lower misuse and abuse potential.

Atomoxetine has an FDA indication for adult ADHD. Atomoxetine is often thought of as the first-line medication for adult ADHD in patients with a history of substance use disorder. There are several studies that demonstrate an improvement in quality of life ratings, for example, with longer term use in patients with ADHD. Atomoxetine selectively inhibits norepinephrine reuptake and medications with this mechanism of action convey a risk of psychosis and mania, especially in patients with a personal or family history of bipolar disorder or psychosis. Like many medications with an antidepressant-like mechanism of action, atomoxetine has a black box warning for increased suicidality in children, adolescents and young adults.

Bupropion does not have an FDA indication for ADHD, though there are meta-analyses that suggest it has some utility. Bupropion is FDA-approved for major depressive disorder. The symptom of poor concentration can be magnified when patients with ADHD experience a major depressive episode. For some of these patients, bupropion might help both disorders. Providers should keep in mind, however, that bupropion is not effective for anxiety disorders. Moreover, some patients with anxiety disorders find that bupropion worsens their anxiety symptoms. Like atomoxetine, bupropion has a black box warning for suicidality in patients under the age of 25. Bupropion can also cause mania and psychosis, particularly in patients with a personal or family history of bipolar disorder or psychosis. Bupropion can increase the risk of seizure and is contraindicated in patients with eating disorders.

While guanfacine has an FDA indication for pediatric ADHD, it does not have an FDA indication for adult ADHD. Some authors are pessimistic about its utility in adult ADHD. Overall, the data is mixed and there have only been a few controlled studies, though research is actively being done and the efficacy (or lack thereof) of guanfacine in adult ADHD may be more clearly articulated in the next few years. Guanfacine is an alpha-2 agonist that is used to treat hypertension and thus it has a unique side effect profile compared to atomoxetine or bupropion.

If you are considering using any of the medications discussed above, please first review your own reference material for full details on side effects, dosing, adjustment in the setting of renal or hepatic impairment, cautions/contraindications, monitoring requirements, and safety in pregnancy and lactation. We most often use Micromedex, UpToDate, or Epocrates. Additionally, there are free databases available to Washington State providers at https://heal-wa.org/professions/. You can also call the Psychiatry Consultation Line (877-927-7924) for clinical advice on using these medications in the treatment of adult ADHD as well as assessment, treatment decisions and monitoring of mental health conditions in general. Even in complicated clinical scenarios, discussing a patient’s care with a colleague can lead to a path forward.

Author
Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatry Consultation Line

Learn More
Cognitive Behavioral Therapy (CBT) for adult ADHD: does ADHD need therapy (pdf)
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Kristen Lindgren, PhD, ABPP
The objectives of this presentation are to 1) review diagnostic criteria for ADHD, 2) understand the Role of CBT in the Treatment of adult ADHD, and 3) describe how combined medication and CBT can benefit adults with ADHD

Treating ADHD in SUD patients: how do I treat patients with ADHD and SUDs without making them addicted to stimulants? (pdf)
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Robert Sise, MD, MBA, MPH
The objectives of this presentation are to 1) review general considerations in diagnosis of adult ADHD, 2) explore multimodal treatment for adult ADHD with co-occurring SUDs, 3) discuss risks and benefits of pharmacotherapy, and 4) explore how ADHD treatment should be coordinated with SUDs treatment.

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Treating Generalized Anxiety Disorder with buspirone

Posted on
500

A common question to the Psychiatry Consultation Line is around treatment of Generalized Anxiety Disorder (GAD) in patients with a history of substance use disorders and for whom a Selective Serotonin Reuptake Inhibitor has not been effective. First-line treatments for Generalized Anxiety Disorder include Cognitive Behavioral Therapy (CBT), Serotonin Reuptake Inhibitors (SRI), or a combination of both. In cases where adjunctive CBT and multiple trials of SRIs have failed, buspirone can be given some consideration.

In 1980s-era, double-blind studies of GAD, buspirone’s efficacy was shown to be similar to benzodiazepines. An important difference between benzodiazepines and buspirone is that it takes buspirone longer to start working. Buspirone requires a multi-week or multi-month trial to assess efficacy. Compared to benzodiazepines, buspirone is less likely to cause sedation and, importantly, is not associated with the development of tolerance or dependence. Common side effects of buspirone include dizziness, nausea, and headache.

The FDA max dosing is 60mg/day and while some patients require a high dose, average therapeutic doses are in the range of 20 to 45 mg/day. Buspirone has a short half-life and some patients benefit from TID dosing.

Please refer to your own reference material for full prescribing information regarding medication dosing, risks, benefits, side effects, monitoring requirements, and drug interactions. We most often use Micromedex, UpToDate, or Epocrates. Additionally, there are free databases available to Washington State providers at https://heal-wa.org/professions/.

Author
Ryan Kimmel, MD
Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Chief of Psychiatry, University of Washington Medical Center
Medical Director, Psychiatric Consultation Line

Learn more
How do I address emerging anxiety during substance use recovery?  (pdf)
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Mark Duncan, MD
The objectives of this presentation are to 1) discuss characteristics between a substance induced anxiety disorder and a primary anxiety disorder, and 2) to talk through different treatment options for anxiety symptoms.

CBT for Anxiety (CBT-A): What can I do with my patient instead of giving them a PRN benzodiazepine?  (pdf)
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Patrick Raue, PhD
The objectives of this presentation are to 1) understand the CBT model of anxiety symptoms, 2) describe how to give the “treatment pitch” to patients, and discuss the difference between treatment with exposure vs. anxiety management strategies, 3) understand how to develop and work on an exposure hierarchy with patients and 4) describe anxiety management strategies that use physical and cognitive approaches.

Anxiety: fast facts and skills for the primary care physician  (pdf)
UW Psychiatry and Addictions Case Conference series (UW PACC)*
Presenter: Ryan Kimmel, MD
A brief overview of diagnosing and treating anxiety in primary care.

*The UW Psychiatry and Addictions Case Conference series (UW PACC) is a free, weekly teleconference that connects community providers with UW Medicine psychiatrists and addictions experts. Sessions include both an educational presentation on an addictions or psychiatry topic and case presentations where providers who participate receive feedback and recommendations for their patients.

Diagnosing and treating bipolar disorder

Posted on

Clinicians call the Psychiatry Consultation Line with a range of questions about individuals with suspected or diagnosed bipolar disorder, which affects an estimated 4.4% of U.S. adults at some time in their lives. Bipolar disorders, sometimes referred to as manic-depressive disorders, are mood disorders that include manic or hypomanic symptoms and depressive symptoms. Accurate diagnosis of bipolar disorder can be difficult, and once a diagnosis is made, clinicians can face numerous decisions regarding acute episode treatment, maintenance treatment, monitoring response, monitoring for adverse effects, and treatment adjustments. These “points to consider” may help as you encounter similar clinical scenarios.

Assessment and Diagnosis

Common PCL Question: How can I assess for bipolar disorder in my primary care practice?

  • A structured assessment can help collect information that any clinician would need to inform diagnosis of bipolar disorder.
  • The Composite International Diagnostic Interview (CIDI) instrument can contribute to a structured assessment by assessing for lifetime experience of manic symptoms. It is important to remember that positive screening results do not equal a clinical diagnosis. In one study in primary care, about 45% of people screening positive on the CIDI, and 15% of people screening negative, were diagnosed with bipolar disorder by a psychiatrist. However, this instrument can help to collect information that might lead clinicians to ask more questions about bipolar disorder in those with a positive screen. PCL psychiatrists can assist with questions about administering structured tools such as the CIDI.
  • Some clinicians also find it useful to have structured tools to assess age of onset of mood symptoms, past mood symptoms and episodes, peripartum mood symptoms, response to medications including to antidepressant medications, family psychiatric history, drug and alcohol use, and other clinical problems, since historical points other than manic symptoms might raise clinical suspicion for bipolar disorders.

Common PCL Question – What questions can I ask patients about past manic symptoms?

  • One strategy to consider in clinical questioning is to ask about discrete periods of concurrently elevated or irritable mood AND increased energy. Then, once identifying a period when that occurred, inquiring about associated hypomanic or manic symptoms.

Common PCL Question – Is there a bipolar disorder spectrum, and does this apply to my patient?

  • Some individuals experience hypomanic symptoms that do not reach the level of severity of a hypomanic or manic episode.
  • Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification includes categories of cyclothymia (subsyndromal hypomanic and depressive symptoms most days over two years), and Other specified bipolar and related disorder due to short-duration hypomanic episodes (i.e. 2-3 day duration), and insufficient number of hypomanic symptoms to reach episode-level (i.e. 3 symptoms). 
  • Additionally, major depressive episodes in major depression can occur with mixed features (concurrent hypomanic symptoms) though the difference in this case is that the individual with major depression with mixed features has never previously experienced a hypomanic or manic episode.
  • Mood fluctuations or ‘swings’ can occur in the absence of bipolar disorder diagnosis. Consider alternate explanations.
  • Visit Psych Education for more information on bipolar spectrum.

Treatment

Common PCL Question – Where do I start with choosing a medication treatment for a patient diagnosed with bipolar disorder?

  • Consider the current mood state. The most commonly experienced mood state in individuals with bipolar disorder is depression with one or more concurrent hypomanic symptoms.
  • There are relatively few FDA-approved or evidence-based medication treatments for bipolar depression and guideline-suggested first-line treatments include quetiapine, lurasidone, lamotrigine and lithium.
  • A greater number of medication treatment options exist for treatment of manic episodes, and guideline-suggested first-line treatments include lithium, quetiapine, risperidone, olanzapine, divalproex (avoid use of divalproex in women of reproductive potential) and aripiprazole.

Common PCL Question – My patient is diagnosed with bipolar disorder. Can I prescribe treatment with an antidepressant?

  • Uncertainty remains about effectiveness of antidepressant medications in treatment of individuals with bipolar disorder. Expert guidelines suggest avoiding antidepressant treatment when two or more concurrent hypomanic symptoms are present, when past antidepressant treatment was associated with onset or worsening of hypomanic symptoms or anxiety symptoms, during an episode with mixed features or in individuals who experience predominantly mixed features episodes, or as monotherapy.
  • If someone is already taking an antidepressant medication, and is not experiencing remission of depression or is experiencing anxiety symptoms or hypomanic symptoms, a reasonable next step is to taper and discontinue treatment with the antidepressant medication.

Common PCL Question – What can I add to this treatment plan that is not a medication?

  • Consider other treatment options including bright light therapy for bipolar depression (administered in midday rather than upon awakening). This treatment was not associated with treatment-emergent hypomanic symptoms in a clinical trial.
  • Psychotherapy options include treatments specific to bipolar depression, and maintenance treatment psychotherapies including strategies to normalize life patterns to reduce risk of mood episode recurrence and improve quality of life.

Monitoring

Common PCL Question – I started this treatment, what can I do next?

  • When caring for individuals diagnosed with bipolar disorder it is important to monitor the effect of any treatment decision. The patient may also have specific treatment goals to monitor.
  • Mood episode recurrence is common, and subsyndromal mood symptoms can occur chronically, which are associated with recurrence.
  • Monitoring symptom severity and frequency as part of measurement-based care could be accomplished with validated patient-reported measures such as the Patient Health Questionnaire-9 for depressive symptoms, and the newer Patient Mania Questionnaire-9 for manic symptoms.

Common PCL Question – What laboratory studies or other monitoring should I do?

  • Some medication treatments such as lithium, quetiapine and other antipsychotic medications require monitoring treatment for a therapeutic medication serum concentration (lithium and divalproex), and for adverse effects such as serum metabolic studies, weight/ body mass index, tremor, or other motor phenomena such as akathisia or involuntary movements. These measurements are usually done at baseline, and every 3-6 months depending on the clinical circumstance. Some individuals treated with antipsychotic medications should have baseline and interval EKG monitoring to measure QTc interval.

Conclusion
Assessment, diagnosis, treatment selection and monitoring can be complicated when caring for individuals with suspected bipolar disorder.  Psychiatrists on the Psychiatry Consultation Line can help clinicians reason through next steps in assessment, treatment decisions, and monitoring. Even in complicated clinical scenarios, discussing a patient’s care with a colleague can lead to a path forward.

For additional reading on bipolar disorder, visit Psych Education by Dr. Jim Phelps.

Author
Joseph Cerimele, MD
Assistant Professor, University of Washington School of Medicine, Department of Psychiatry and Behavioral Sciences
Director, Psychiatry and Behavioral Sciences Grand Rounds

References
Pacchiarotti I, et al. The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders. Am J Psychiatry. 2013;170:1249-1262.

Goodwin GM, et al.  Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30:495-553.

Yatham LN, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. 2018;20:97-170.

Cerimele JM, et al. Bipolar disorder and PTSD screening and telepsychiatry diagnoses in primary care. Gen Hosp Psychiatry. 2020;65:28-32.

Cerimele JM, et al. The Patient Mania Questionnaire (PMQ-9): a Brief Scale for Assessing and Monitoring Manic Symptoms. J Gen Intern Med. 2021; Jun 18. doi: 10.1007/s11606-021-06947-7. Online ahead of print.