Shrinks In Sneakers

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  • Olanzapine Fluoxetine Combination Symbyax: The OG of Bipolar Depression Treatment 

    Olanzapine Fluoxetine Combination Symbyax: The OG of Bipolar Depression Treatment 

    Introduction

    The olanzapine fluoxetine combination was FDA approved in 2003 for the treatment of depressive episodes in bipolar I disorder. In 2009 it was granted approval for treatment resistant depression. 

    This medication consists of the atypical dopamine blocking medication olanzapine and the SSRI fluoxetine. Many people consider olanzapine to be the best antipsychotic not named clozapine (see my video on the best antipsychotic in the world). This comes from the CATIE study where olanzapine proved to be superior to other medications. It has good efficacy, once daily dosing at night, and low risk for cardiac conduction abnormalities (QTc prolongation). However, the side effects including risk for weight gain and metabolic complications have made it a second line option. 

    My residents often jump to this medication on the inpatient unit, but I usually tell them to use caution because of the side effects and should it not be effective, it leaves you with clozapine as the next option in terms of effectiveness. 

    Fluoxetine is an antidepressant that has been around a long time with a broad spectrum of indications. It’s long track record and safety profile makes it a go to antidepressant in both the adult and child adolescent populations. Its main disadvantage is drug interactions. 

    Dosing

    People often think you can make this medication by simply combining olanzapine and fluoxetine and do not believe you need to use the brand name combination pills. I would use some caution with that approach. 

    When we look at the doses in the combination pill, they are ones that are difficult to make with the current available dosages. For example, olanzapine comes in 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and finally 20 mg doses. 

    The fixed-combination capsule (olanzapine/fluoxetine) comes in 3/25 mg, 6/25 mg, 12/25 mg, 6/50 mg, 12/50 mg. The studies leading to approval of this medication were conducted using these doses in a fixed combination. It’s not clear that dosing each individually is effective. 

    How to Start the Medication

    For bipolar depression the olanzapine fluoxetine combination should be started at 6/25 mg dosed at bedtime. With a target dose of 6-12/25-50 mg depending on clinical response. 

    Labs prior to starting the medication: 

    You should have a baseline weight, waist circumference, blood pressure, fasting glucose and lipid profile prior to starting the medication 

    Cost

    The combination pill is more expensive than either medication alone. According to Good Rx The 6/25 mg capsule is $140-$150 per month. This is compared to olanzapine 5 mg which costs $9.00 and fluoxetine 20 mg which costs $4.00 

    Side Effects

    Olanzapine: Most common is somnolence (dose related), dry mouth (dose related), constipation (anticholinergic), weight gain (up to 40% incidence and 10-30 lbs. of weight gain is common), increased appetite, EPS (dose related). 

    Fluoxetine: Nausea, diarrhea, nervousness, abnormal dreams, weight loss, sweating, tremor, sexual side effects, rash, and headaches. Rare increased risk for bleeding when combined with NSAIDs and hyponatremia in the elderly due to SIADH. 

    Mechanism of action 

    Olanzapine: Dopamine D-2 and 5-HT2A antagonist that is metabolized by CYP1A2 and CYP2D6 

    Fluoxetine: serotonin reuptake inhibitor that is metabolized by CYP2D6 and is an inhibitor of CYP 2C9/2C19 and 2D6 with a half-life of 4-6 days and 9 days for the metabolite norfluoxetine 

    The half-life is important here because what happens when someone stops taking the medication? The olanzapine has a much shorter half-life and will be cleared from the body more rapidly leaving the person exposed to fluoxetine without a mood stabilizing element possibly inducing mania or worsening mood symptoms. This is something to be mindful of when using this combination. 

    Studies Showing Efficacy

    The studies that resulted in FDA approval for bipolar depression in 2003 were short, 8 weeks in duration. A total of 833 patients with bipolar I depression received either olanzapine alone, olanzapine fluoxetine combination (OFC), or placebo. Patients on OFC and olanzapine alone showed a significant reduction in depressive symptoms compared to placebo as early as the end of week 1 of treatment. By the end of 4 weeks the OFC participants saw significantly more improvement than placebo or olanzapine alone. The superiority continued over the final 4 weeks of the study. By the end 24.5% of patients on placebo met remission criteria, 32.8% of the olanzapine only group achieved remission, and 48.8% of the OFC group achieved remission. 

    For the 2009 approval of OFC in treatment resistant depression, it was based off two eight-week double blind placebo-controlled studies using doses of 6 to 18 mg for olanzapine and 25 to 50 mg for fluoxetine. 40% of patients receiving the OFC responded to therapy Vs 30% and 26% receiving fluoxetine or olanzapine monotherapy. The starting dose was 6/25 mg and could be titrated to 18/75 mg as tolerated. 

  • Boosting the Mind: How Antipsychotics Impact Cognitive Function

    Boosting the Mind: How Antipsychotics Impact Cognitive Function

    Antipsychotic Drugs and Cognitive Function: Key Findings from a Systematic Review and Meta-Analysis

    Background:
    Cognitive impairment is a core feature of schizophrenia, often leading to significant functional disability. Antipsychotic medications are the main treatment for schizophrenia, but their impact on cognitive function remains debated.

    Objective:
    This systematic review and network meta-analysis aimed to compare the effects of different antipsychotic drugs on cognitive function in patients with schizophrenia.

    Methods:
    The review included randomized controlled trials (RCTs) that assessed cognitive outcomes in patients with schizophrenia treated with antipsychotics. A network meta-analysis was conducted to compare the cognitive effects across different antipsychotic drugs.

    Key Findings:

    1. Cognitive Improvement:
      • All antipsychotics studied showed modest cognitive benefits, though the effect sizes were small.
      • Second-generation antipsychotics (SGAs) generally performed better than first-generation antipsychotics (FGAs).
      • Among SGAs, lurasidone and amisulpride demonstrated the most pronounced cognitive improvements.
      • FGAs like haloperidol showed the least benefit for cognitive function.
    2. Domains of Cognitive Improvement:
      • The drugs improved different cognitive domains, including working memory, processing speed, and executive functioning, though no single drug showed superiority across all domains.
    3. Comparative Effectiveness:
      • In head-to-head comparisons, lurasidone and amisulpride were consistently ranked higher for cognitive improvement.
      • Olanzapine and risperidone also showed beneficial effects, though to a lesser extent.
    4. Adverse Effects and Tolerability:
      • Cognitive improvements were often seen alongside side effects, with some drugs (e.g., olanzapine) associated with metabolic risks that may counterbalance cognitive benefits.
    5. Limitations:
      • The analysis emphasized the small effect sizes, suggesting that while antipsychotics may slightly improve cognition, the changes may not be clinically meaningful in many cases.
      • Cognitive rehabilitation therapies may need to be paired with pharmacological treatment for more significant cognitive gains.

    Conclusions: While antipsychotics can modestly improve cognitive function in schizophrenia, the benefits are relatively small, and no drug significantly outperforms others across all cognitive domains. Lurasidone and amisulpride may offer the greatest cognitive benefits, but additional interventions may be necessary to address cognitive deficits effectively.

  • Want to Slow Parkinson’s Progression? Consider the TEMPO-3 Breakthrough

    Want to Slow Parkinson’s Progression? Consider the TEMPO-3 Breakthrough

    The TEMPO-3 trial focused on the use of rasagiline in patients with early Parkinson’s disease (PD). Rasagiline is a monoamine oxidase-B (MAO-B) inhibitor, which helps to increase dopamine levels by preventing its breakdown, potentially slowing the progression of Parkinson’s disease. Here are the key findings from the TEMPO-3 trial:

    1. Slowed Progression of Symptoms: The trial found that early treatment with rasagiline at a dose of 1 mg/day slowed the progression of motor symptoms compared to delayed treatment, suggesting potential disease-modifying effects.
    2. Improvement in Quality of Life: Patients who received rasagiline earlier in their treatment course experienced an improvement in daily activities and quality of life. This was measured by tools such as the Unified Parkinson’s Disease Rating Scale (UPDRS).
    3. Well-Tolerated: Rasagiline was well-tolerated with a favorable safety profile. The side effects were mild and included headache, joint pain, and flu-like symptoms, but there were no significant safety concerns over the course of the trial.
    4. Delay in Disability: The study hinted at rasagiline’s ability to delay the onset of disability by slowing motor symptom progression, which may result in a reduced need for other symptomatic treatments earlier in the disease course.

    Overall, the TEMPO-3 trial supported rasagiline’s role as a first-line therapy in early Parkinson’s, emphasizing its benefit in delaying motor progression and potentially altering the disease course.

  • The Culture of Burnout in Modern Medicine

    The Culture of Burnout in Modern Medicine

    Modern medicine has given rise to a new culture of burnout. As physicians, we are already high achievers—it’s a prerequisite to make it through the intense training. However, this constant push for relentless productivity often leads to feelings of exhaustion and disconnection. In medicine, the focus is always on doing more—seeing more patients, finishing more tasks, and achieving more outcomes each day.

    With digital technology, we’re constantly connected, always on call. Patients, colleagues, and administrators reach out through calls, texts, and emails at all hours. The pressure to respond immediately leads to guilt when we can’t meet these demands, even when they’re unreasonable. The result? We push ourselves beyond our limits, sacrificing our own well-being in the process.

    This grind leaves little room to rest or tend to our mental health. The importance of downtime is overlooked, even though it’s essential for long-term sustainability in our profession. But it’s time we rethink the culture of busyness and productivity. We need to start focusing on slowing down, with an emphasis on not staying busy for the sake of being busy.

    If you’re like me, you’ve probably tried this, only to find your mind immediately wandering to the next thing you need to do. The challenge is real. But to reclaim a deeper sense of meaning and purpose in both our personal and professional lives, we must commit to this change. By slowing down, we can begin to find more peace, love, and joy in our day-to-day activities.

    Let’s reclaim our lives—it’s long overdue

  • Contingency Management: The Overlooked Game-Changer for Methamphetamine Use Disorder

    Contingency Management: The Overlooked Game-Changer for Methamphetamine Use Disorder

    I frequently encounter patients with methamphetamine use disorder, and I don’t know about you, but finding effective interventions in the inpatient psychiatric setting can be a real challenge. Unlike opioid or alcohol use disorders, where we have biological interventions like buprenorphine or naltrexone, methamphetamine use disorder lacks such clear pharmacological treatments. Because of this, many rehab facilities are reluctant to admit patients whose primary issue is methamphetamine use.

    In my practice, I often turn to combinations like bupropion and naltrexone since they’re among the few studied pharmacological options for methamphetamine use disorder. However, based on my experience, the results are modest at best—but I suppose it’s better than nothing.

    That said, there’s a much simpler, evidence-based option that doesn’t even require inpatient treatment, and it’s been around since the 1980s: Contingency Management. The concept is straightforward: reward patients with small incentives—like gift cards worth $30 or less—for each negative drug screen they produce. As patients continue to test negative, the rewards increase. This approach has been shown to double the chances of success in stopping methamphetamine use.

    Of course, there are potential issues, such as concerns about fraud or patients providing fake samples. But let’s be real—how much are we already spending on treating methamphetamine users without seeing much improvement? Probably a lot more. With contingency management, we’re not just spending money—we’re actually seeing patients get better.

  • MAOIs: Mechanism of Action, Common Medications, and Side Effects

    MAOIs: Mechanism of Action, Common Medications, and Side Effects

    Mechanism of Action

    Monoamine oxidase inhibitors (MAOIs) are a class of medications primarily used to treat depression. They work by inhibiting the activity of monoamine oxidase enzymes (MAO-A and MAO-B). These enzymes are responsible for breaking down neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain. By inhibiting these enzymes, MAOIs increase the levels of these neurotransmitters, which can help improve mood and alleviate depressive symptoms.

    Common Medications

    1. Phenelzine (Nardil)
    2. Tranylcypromine (Parnate)
    3. Isocarboxazid (Marplan)
    4. Selegiline (Emsam) – Available as a transdermal patch

    Side Effects

    MAOIs can have significant side effects and interactions, which is why they are often not the first choice for treating depression. Some common side effects include:

    1. Hypertensive Crisis: Consuming foods high in tyramine (such as aged cheeses, cured meats, and fermented products) can cause dangerously high blood pressure.
    2. Orthostatic Hypotension: A sudden drop in blood pressure when standing up, leading to dizziness or fainting.
    3. Insomnia: Difficulty falling or staying asleep.
    4. Weight Gain: An increase in body weight over time.
    5. Sexual Dysfunction: Decreased libido, erectile dysfunction, or difficulty achieving orgasm.
    6. Headaches: Frequent or severe headaches.
    7. Edema: Swelling, particularly in the lower limbs.
    8. Fatigue: General feeling of tiredness or lack of energy.
    9. Dry Mouth: Reduced saliva production, leading to a dry sensation in the mouth.

    Precautions

    • Dietary Restrictions: Due to the risk of hypertensive crisis, patients on MAOIs must follow strict dietary restrictions to avoid tyramine-rich foods.
    • Drug Interactions: MAOIs can interact with numerous medications, including over-the-counter drugs, other antidepressants, and certain pain medications, potentially leading to severe or life-threatening conditions.
    • Medical Monitoring: Regular monitoring by a healthcare professional is essential to manage and mitigate potential side effects and interactions.

    MAOIs can be effective for certain patients, particularly those who have not responded to other antidepressant treatments. However, their use requires careful management due to their side effect profile and interaction potential.

  • Non-Harvard Trained: Real Care, Real Results

    Non-Harvard Trained: Real Care, Real Results

    I constantly come across the phrase “Harvard-trained” in people’s bios. Sure, it brings instant brand recognition and credibility. But in reality, being trained at a prestigious institution—even one like Harvard—doesn’t automatically mean better skills or superior patient care.

    In psychiatry, quality care is shaped by much more than where someone trained. It comes from clinical experience, empathy, lifelong learning, and the ability to genuinely connect with patients. These are the factors that truly define the impact we make.

    While training is important, the real measure of a psychiatrist’s ability is in the care they provide and the outcomes they achieve. Psychiatry is such a nuanced field that no amount of prestige can substitute for hands-on experience and genuine compassion.

    It’s unfortunate that where someone trained is often used as a superficial marker of competence, overshadowing the true work that goes into patient care. Personally, I’d reject a Harvard offer, because for me, it’s about one thing: providing the highest level of care possible, every single day.

  • The more I learn the less certain I am About Things

    The more I learn the less certain I am About Things

    Did you ever feel like the more you learn the less certain you are about things?

    It’s completely natural to feel this way, especially in a field as complex and evolving as psychiatry. Uncertainty and skepticism can be strengths, driving you to seek deeper understanding and remain open to new perspectives and evidence. Here are a few thoughts that might resonate

    Complexity of Human Mind: The human brain and psyche are incredibly complex, and our understanding is still in its infancy. This complexity can make definitive answers elusive.

    Evolving Science: Psychiatry, like all medical fields, is constantly evolving. New research can change our understanding of mental health conditions and treatments, making certainty difficult.

    Individual Differences: What works for one person might not work for another. This variability can make it hard to be sure about diagnoses and treatments.

    Holistic Approach: Embracing uncertainty can lead to a more holistic approach, considering biological, psychological, and social factors in diagnosis and treatment.

    Continuous Learning: Your skepticism can fuel a commitment to continuous learning and improvement, which is essential in providing the best care.

    Collaboration and Discussion: Engaging in discussions with colleagues who have different perspectives can be enriching and help balance your skepticism with practical insights.

    Patient-Centered Care: Uncertainty can remind you to listen to your patients’ experiences and perspectives, which can be as important as clinical knowledge in guiding treatment.

    It’s good to question and explore; it means you’re thoughtful and committed to truly understanding and helping your patients.

  • Unintended Outcomes After FDA Pediatric Antidepressant Warnings

    Unintended Outcomes After FDA Pediatric Antidepressant Warnings

    The article “Intended and Unintended Outcomes After FDA Pediatric Antidepressant Warnings: A Systematic Review” examines the effects of the FDA’s 2003-2004 black box warning on antidepressants regarding the risk of increased suicidal thoughts and behaviors in children and adolescents.

    Intended Outcome:

    • The FDA issued the warning to ensure greater awareness of potential risks, encouraging careful monitoring of pediatric patients taking antidepressants.
    • The goal was to reduce suicidal behaviors potentially linked to antidepressant use in younger populations.

    Unintended Outcomes:

    • The warning led to a significant drop in antidepressant prescriptions for children and adolescents.
    • There was a corresponding increase in untreated depression, which may have led to higher rates of suicide attempts and worsening mental health outcomes in some cases.
    • Reduced prescriptions were associated with a decrease in diagnosis and treatment of mood disorders in pediatric populations.
    • The warning inadvertently caused confusion among healthcare providers and parents, often resulting in delays in seeking treatment for depression or anxiety.

    Post-Warning Trends:

    • Follow-up research found no consistent evidence that the use of antidepressants in pediatric patients increases the risk of completed suicides.
    • The decline in antidepressant use and increase in suicidal behaviors during the period following the warning suggest unintended negative consequences of the FDA’s decision.

    Conclusions:

    • While the warning achieved its goal of raising awareness about the risks of antidepressants in children, it also resulted in under-treatment of depression, potentially exacerbating mental health challenges.
    • The article calls for balanced decision-making in pediatric antidepressant use, emphasizing the need for risk-benefit assessments and careful monitoring rather than outright avoidance of antidepressants.

      The FDA’s black box warning led to a reduction in antidepressant use but also to increased untreated mental illness, highlighting the complexities of addressing medication risks in vulnerable populations.

    1. Let’s Invest In Mental Health

      Let’s Invest In Mental Health

      World Mental Health Day:

      World Mental Health Day is a reminder that mental health is not just important—it’s essential. There’s a saying, “There is no health without mental health,” and I couldn’t agree more. One of the leading causes of disability in the United States is untreated mental health conditions. Yet, we face a mental health crisis, largely because we continue to avoid investing in proper treatment.

      It doesn’t make sense to ignore mental health, only to pay heavily later on. By focusing on early intervention and accessible care, we could improve countless lives and reduce the long-term costs that come from untreated conditions. It’s not glamorous, it won’t make anyone rich overnight, but it will undeniably make the world a better place—and that, in itself, pays dividends for everyone.

      This World Mental Health Day, let’s commit to giving mental health the attention and investment it truly deserves.