Shrinks In Sneakers

Tag: bipolar disorder

  • Clearing the Smoke: What We Know About Cannabis for Mental Health Treatment

    Clearing the Smoke: What We Know About Cannabis for Mental Health Treatment

    Research into the therapeutic potential of cannabis for mental health disorders has grown in recent years, with mixed findings from randomized controlled trials (RCTs).

    Anxiety Disorders

    • CBD (Cannabidiol) has shown promise in reducing anxiety symptoms in RCTs, particularly for social anxiety disorder (SAD). For instance, a small RCT found that a single dose of 300 mg of CBD reduced anxiety levels in participants undergoing a simulated public speaking test.
    • Some RCTs suggest that CBD may be anxiolytic without causing impairment or euphoria, making it preferable for anxiety compared to THC-dominant cannabis products, which may exacerbate anxiety in some users.

    Post-Traumatic Stress Disorder (PTSD)

    • RCTs exploring THC and CBD combinations in PTSD have had mixed outcomes. Some studies indicate that THC may reduce nightmares and improve sleep in PTSD patients, though these findings are generally based on small sample sizes and short-term trials.
    • A recent RCT with a synthetic cannabinoid (nabilone) reported some symptom improvement in PTSD-related insomnia and nightmares. However, larger trials with longer follow-ups are necessary to clarify the efficacy and safety for PTSD.

    Depression

    • Few RCTs show consistent evidence supporting cannabis (CBD or THC) as an effective treatment for major depressive disorder. Some trials indicate that CBD may have antidepressant-like effects, possibly due to serotonin receptor activity, but more robust and long-term studies are needed.
    • Concerns persist over THC’s potential to exacerbate depressive symptoms, particularly with regular or heavy use.

    Schizophrenia and Psychotic Disorders

    • THC-dominant products have been associated with increased risk of psychosis and exacerbation of symptoms in people predisposed to psychotic disorders. This has led to caution against THC use in people with schizophrenia.
    • CBD has shown promise as an adjunctive treatment in some RCTs, with findings suggesting that it may have antipsychotic effects without the psychoactive effects of THC. For example, an RCT found that CBD reduced psychotic symptoms and improved cognitive function when added to standard antipsychotic treatment, though the effects were modest.

    Bipolar Disorder

    • Evidence from RCTs on the use of cannabis in bipolar disorder is sparse and generally negative. Some trials indicate that THC may worsen manic and depressive symptoms in bipolar patients, and there is little to no support for cannabis as a treatment for bipolar depression.

    Sleep Disorders

    • Some RCTs have evaluated cannabinoids for sleep disturbances, with CBD showing potential for improving sleep quality. However, THC may reduce REM sleep, which could impact sleep architecture negatively over time.
    • For PTSD-related insomnia, cannabinoids like nabilone have shown some benefit, but the effects on sleep in general populations remain uncertain.

    Limitations

    • Sample Sizes and Duration: Many RCTs are small and short-term, limiting the generalizability and understanding of long-term effects.
    • Dosing and Formulations: Variability in cannabinoid content (THC vs. CBD), formulations (edibles, oils, vapes), and dosages across studies makes comparison challenging.
    • Side Effects: Both CBD and THC can have side effects, though THC’s psychoactive properties can lead to cognitive impairment, addiction potential, and negative impact on mood in some patients.

    While CBD shows some promise in anxiety, PTSD, and psychotic disorders, RCT evidence for other mental health conditions remains inconclusive or even negative, especially with THC. Further large-scale, long-term RCTs are needed to establish the efficacy and safety profile of cannabis-based treatments in mental health.

  • Lurasidone vs. Quetiapine: Which Will Emerge as the Top Choice for Bipolar Depression?

    Lurasidone vs. Quetiapine: Which Will Emerge as the Top Choice for Bipolar Depression?

    Bipolar depression is a challenging and common condition, with limited options for effective medication management. Finding the best treatment can be tough, especially given the lack of high-quality head-to-head comparisons in the literature. Two frequently prescribed medications for bipolar depression, quetiapine and lurasidone, are both solid options—but is one truly superior to the other?

    Head-to-head randomized controlled trials comparing lurasidone and quetiapine specifically for bipolar depression are relatively limited. However, both medications have established evidence in treating bipolar depression, with some distinctions in efficacy, safety, and tolerability that can be informative for comparison.

    1. Efficacy: Studies suggest that both lurasidone and quetiapine are effective in treating depressive symptoms in bipolar disorder. Quetiapine, particularly at doses of 300 mg or 600 mg, has shown significant efficacy in reducing depressive symptoms, whereas lurasidone also demonstrates effectiveness at doses typically ranging from 20 mg to 120 mg. Head-to-head trials generally find comparable efficacy between the two, though quetiapine may be preferred in certain cases for its sedative effects, which can help with associated insomnia in bipolar depression.
    2. Tolerability and Side Effects: Lurasidone tends to have a more favorable side effect profile, with a lower risk of weight gain, metabolic issues, and sedation compared to quetiapine. Quetiapine is often associated with more sedation and metabolic side effects, such as weight gain and increased cholesterol and triglycerides, which may be more pronounced at higher doses. Lurasidone’s side effect profile may make it a better option for patients where weight gain or sedation is a concern.
    3. Functioning and Quality of Life: Some studies highlight that patients on lurasidone report better functioning and fewer sedative effects, which may positively impact quality of life, particularly for those sensitive to the sedative properties of quetiapine.
    4. Dropout Rates: Due to quetiapine’s sedative side effects, some patients discontinue it more often than lurasidone. Lurasidone’s lower risk for sedation and weight gain tends to improve adherence for those struggling with quetiapine’s tolerability.

    Both medications are effective for bipolar depression, but lurasidone may be better tolerated overall, especially concerning weight gain and sedation. We should not forget that lurasidone carriers an equally concerning side effect of akathisia which can also increase dropout rates especially at higher doses. Additional direct head-to-head trials would be valuable to further elucidate these findings.

  • 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. 

  • Breakthrough in Bipolar Detection: Promising, But Is It Practical

    Breakthrough in Bipolar Detection: Promising, But Is It Practical

    While this study underscores the critical need for early detection of bipolar disorder to prevent misdiagnosis and improper treatment, the advanced MRI techniques and extensive behavioral assessments it highlights may not be practical in most current clinical settings. This is often the challenge with such research: although it can enhance diagnostic accuracy, its real-world application remains limited.

    Link to Article: https://pubmed.ncbi.nlm.nih.gov/39069165/

  • ECT Maintenance: To Continue or Not To Continue

    ECT Maintenance: To Continue or Not To Continue

    The article on Clinical Outcomes of Continuation and Maintenance Electroconvulsive Therapy (ECT) highlights the role of ECT in preventing relapses in patients with major depressive disorder. Continuation (C-ECT) and maintenance (M-ECT) ECT, when used after an initial successful acute ECT response, are shown to be effective in reducing the recurrence of mood disorders, particularly when combined with pharmacotherapy. Despite its proven benefits, this therapeutic approach is underutilized. Studies also suggest that C-ECT and M-ECT are well-tolerated with no significant cognitive decline​

    Link to the study: https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2823669

  • Rational Polypharmacy and Evidence-Based Off-Label Prescribing: Navigating the Risks of Irrational Treatment

    Rational Polypharmacy and Evidence-Based Off-Label Prescribing: Navigating the Risks of Irrational Treatment

    Today’s post is more of a clinical reflection. I’ve been sharing a lot about research studies lately, but I want to pause and talk about polypharmacy in psychiatry and off-label prescribing. Have you ever been in a situation where a patient comes in, and as you review their medications, you see they’re taking a benzodiazepine for anxiety, an antidepressant for depression, a dopamine blocker for psychosis, and a mood stabilizer for mood swings? Maybe even a stimulant for ADHD is thrown in the mix. While I say that with some humor, in reality, this is a common scenario. As an educator, it’s crucial to discuss rational polypharmacy and evidence-based off-label prescribing, as well as the dangers of irrational, off-evidence prescribing.

    There are times when using more than one dopamine-blocking medication is necessary in the short term—I’ve done it myself to achieve short-term stabilization—but it would never be my long-term plan. Treatment resistance is another situation where off-label medication, if supported by evidence, could be beneficial. However, if none of these justifications apply and the patient isn’t improving, yet they’re on a potentially risky combination of medications, this is the moment to reconsider the diagnosis. It may sound surprising, but misdiagnosis in psychiatry happens often. If the patient isn’t getting better, it could be because you’re treating the wrong condition.

    It’s also possible that you’re addressing a disorder that isn’t the primary issue. For example, a patient being treated for ADHD may have attention and impulsivity problems, but these could actually stem from an underlying bipolar disorder. Since symptoms in psychiatry frequently overlap across multiple disorders, it’s essential to maintain a diagnostic hierarchy in your mind. Sorting out which disorder should be prioritized can often resolve other symptoms that might be masquerading as a different psychiatric condition.

    So, if treatment isn’t working and the medication list keeps growing, consider that there may have been a mistake in the diagnosis, or that the focus has been on the wrong condition. Often, many symptoms are driven by a more serious underlying disorder, like bipolar disorder.

  • From Trip to Trigger: The Schizophrenia Risk After Substance-Induced Psychosis

    From Trip to Trigger: The Schizophrenia Risk After Substance-Induced Psychosis

    I recently had an interesting discussion with one of our residents about the risk of developing schizophrenia after experiencing substance-induced psychosis. The conversation was sparked by a study based on data from the Danish Civil Registration System. Fun fact: when you see large data sets like this, they’re often from Scandinavian countries.

    The study followed 6,788 people who were diagnosed with substance-induced psychosis between 1994 and 2014. They tracked patients until they developed schizophrenia, bipolar disorder, or passed away, using statistical methods to calculate the risk of conversion to a serious mental illness.

    A key takeaway: this study didn’t just look at the risk of schizophrenia but also included bipolar disorder and various substances—not just cannabis. Overall, 32.2% of people with substance-induced psychosis went on to develop either schizophrenia or bipolar disorder. Cannabis-induced psychosis had the highest conversion rate, with 47.4% of those cases developing one of these disorders.

    Being young and male increased the likelihood of developing schizophrenia, and self-harm after substance-induced psychosis was also linked to a higher risk of both schizophrenia and bipolar disorder.

    The big takeaway here? Substance-induced psychosis is closely associated with the development of serious mental illnesses. Follow-up care is essential, and steering clear of cannabis is always a smart move.

    Link to the article: https://psychiatryonline.org/doi/10.1176/appi.ajp.2017.17020223

  • Gabapentin/Neurontin The Most Common off-Label Prescription in Psychiatry 

    Gabapentin/Neurontin The Most Common off-Label Prescription in Psychiatry 

    Introduction 

    Gabapentin is approved by the FDA for three specific indications to prevent and control partial seizures, relieve nerve pain following shingles (post herpetic neuralgia), and to treat moderate to severe restless leg syndrome. Unfortunately, less than 1% of the prescriptions written for gabapentin are for the above listed FDA approvals. In fact, much of the off-label prescribing of gabapentin is done for the treatment of psychiatric and substance use disorders. 

    We were first alerted to the misleading marketing practices when Pfizer paid a $2.3 billion dollar fine for misleading clinicians through their marketing campaigns. Gabapentin is often thought of as a benign medication that can address symptoms in several common disorders including migraine, chronic pain, fibromyalgia, opioid use disorder, anxiety, and mood disorders. There is now mounting evidence that this medication is not as safe as people once assumed yet many of these prescribing practices continue despite a lack of quality data. Today we will review the safety and efficacy of gabapentin in psychiatric disorders. 

    How Does Gabapentin Work?

    Gabapentin functions by binding to the alpha-2-delta subunit of voltage gated calcium channels theoretically offering antipain, anticonvulsant, and anxiolytic properties. Although it’s structurally related to the GABA neurotransmitter, there is no direct interaction at GABA A or B receptors. 

    Why is there such an increase in Gabapentin prescribing?

    In the United States the opioid epidemic drove much of the 64% increase in gabapentin prescriptions 2012 to 2016 as policy makers searched for safer alternatives for pain management. Although lacking any data for the treatment of chronic pain, gabapentin was elevated into this role because of several factors cost, non-controlled status at the federal level, evidence in neuropathic pain, and benign side effect profile. 

    However, the risk for gabapentin abuse became apparent as more prescriptions were written. The risk of adverse effects was prevalent when combined with other CNS depressants such as opioids, the exact thing gabapentin set out replace. Approximately 15%-22% of people with an existing substance use disorder abuse gabapentin. Those who overused gabapentin were found to be at increased risk of all-cause or drug-related hospital stay and emergency visits for altered mental status and respiratory depression. 

    The off-label prescribing of gabapentin comes with risk. 

    Evidence For Use in Anxiety Disorders

    The evidence for gabapentin’s use in anxiety disorders comes from only two industry sponsored studies with a total of 172 participants. These are relatively small but well-designed studies that provide limited evidence for the use of gabapentin in anxiety disorders. The first study was in 1999 and looked at the use of gabapentin in social anxiety disorder. 69 participants were randomized to placebo or gabapentin 900-3600 mg/day for 14 weeks. A significant reduction in social anxiety was observed over the 14 weeks and the conclusion was more studies were needed to confirm the results. The other study looked at panic disorder with the same study design and doses of gabapentin, only this time the study lasted 8 weeks. The results indicated gabapentin was effective for severe panic disorder. One thing we notice is neither of these studies focused on generalized anxiety disorder. These results have not been replicated in other studies. 

    There is far more evidence for the use of pregabalin in anxiety disorders. In Europe it does have regulatory approval for generalized anxiety disorder. 

    Evidence For Use in Bipolar Disorder 

    I’m going to burst this bubble and maybe a few other bubbles up front. While some believe all anticonvulsants are “mood stabilizers” they are wrong. Gabapentin has never proven in RCTs to treat mania or any other aspect of bipolar disorder. Likewise, Topiramate and oxcarbazepine have performed poorly in studies assessing their efficacy in bipolar disorder. Simply put, if you are on any of the three medications as primary mood stabilizers it’s best to consider other options such as lithium. 

    Evidence For Use In Alcohol and Cannabis Use Disorder  

    While addiction treatment is part of the reason we are in this mess with gabapentin, it does have a role in alcohol use disorder (AUD) and cannabis use disorder. The APA added gabapentin as a second line option for AUD because patients who take it for this indication report fewer heavy drinking days with an effect size in the moderate range. There is also some indication that sleep quality improves with gabapentin when patients are cutting back or stopping alcohol use. Alcohol is known to worsen sleep with more frequent nighttime awakenings. The dose range is 300-3600 mg/day in divided doses with many using an average of 900 mg/day. 

    Gabapentin is sometimes used for alcohol withdrawal in place of benzodiazepines or phenobarbital. There were a few seizures in the gabapentin groups raising some questions about its use in severe alcohol withdrawal. It’s probably best left for those with less severe dependence. 

    Typical Taper for Alcohol Withdrawal

    -Start with 1200-2400 mg/day in three divided doses 

    -Taper to 600 mg/day over the course or 4-7 days watching for objective signs of alcohol withdrawal and have Ativan available should a seizure develop. 

    -Taper by 300 mg/day over the next 2-3 days until the medication is completely off. 

    In cannabis use disorder there is limitted data. A single study showed improvement in withdrawal symptoms, reduced cannabis use, and improved executive function but this is not enough to recommend gabapentin on a regular basis in clinical practice. 

    It’s important to note gabapentin failed in controlled trials for cocaine, methamphetamine, benzodiazepine, and opioid use disorder. It’s dangerous to combine gabapentin and opioids as discussed earlier in the video. 

    A Quick Note on Gabapentin for Chronic back pain 

    There are 8 total studies including a systematic review and meta-analysis to assess pain relief in patients with chronic lower back pain a reason many patients tell me they are taking gabapentin for. When you pool this data together, gabapentin demonstrated minimal improvement in pain compared to placebo and had an increase in adverse effects including dizziness, fatigue, and visual disturbances.

    Adverse Effects 

    The most common side effects include sedation, fatigue, dizziness, imbalance, tremor, and visual changes. 

    Dosing

    Gabapentin has a short half-life of 6 hours and will need to be dosed three times per day. The kinetics of gabapentin are not linear which means levels in the blood do not rise consistently. For a 900 mg dose, only 540 mg is absorbed. This has to do with the transporters responsible for gabapentin absorption becoming over saturated limiting the amount of medication absorbed. 

    Conclusion

    While there are very good reasons to consider the use of gabapentin many of the common reasons cited in clinical practice lack the appropriate evidence to support using the medication. It’s best to stick with FDA approved indications and if you are prescribing it off-label consider only using it for the disorders with the most evidence in my opinion that is alcohol use disorder when other treatments have failed. 

  • Lamotrigine/Lamictal is It Really Effective in Bipolar Disorder?

    Lamotrigine/Lamictal is It Really Effective in Bipolar Disorder?

    There are a lot of good things about lamotrigine, and it’s commonly used in both the adult and child adolescent population. The question is how effective is lamotrigine at treating mania, and bipolar depression? I will answer this and provide an in-depth overview of the medication here in this video. Timestamps

    Introduction: 00:00 to 00:35

    Indications and a discussion on negative studies: 00:36 to 04:55

    Mechanism of Action: 04:56 to 06:10

    Dosing: 06:11 to 08:19

    Side Effects: 08:20 to 12:48

    Final Comments: 12:49 to 15:38