Shrinks In Sneakers

Tag: medication

  • Breaking the Trauma Cycle: Can We Prevent PTSD Before It Begins?

    Breaking the Trauma Cycle: Can We Prevent PTSD Before It Begins?

    The use of hydrocortisone and propranolol in the prevention of post-traumatic stress disorder (PTSD) has been explored in several randomized controlled trials (RCTs). We always want to know does it work or is it just another interesting idea with little evidence to support its use

    Hydrocortisone:

    Hydrocortisone, a corticosteroid, has been investigated for its potential to modulate the stress response and prevent the consolidation of traumatic memories, which is thought to contribute to the development of PTSD.

    1. Mechanism: Hydrocortisone works by increasing cortisol levels, which can suppress the stress-induced overactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Cortisol may reduce memory consolidation of trauma, thus decreasing PTSD risk.
    2. RCT Evidence:
      • Schelling et al. (2004) conducted a study on patients in the ICU, where hydrocortisone was used to treat septic shock. They found that patients who received hydrocortisone had a significantly lower risk of developing PTSD symptoms at follow-up compared to the placebo group. This suggested that hydrocortisone might have a protective effect in stress-related conditions.
      • Survivors of trauma: In a study by Zohar et al. (2011), trauma patients who received hydrocortisone in the immediate aftermath of the traumatic event had lower rates of PTSD symptoms compared to those who received placebo. The results suggested that hydrocortisone may reduce PTSD incidence when administered shortly after trauma exposure.
      • Critically ill patients: Schelling et al. (2001) showed that administering hydrocortisone to critically ill patients in the ICU reduced PTSD symptoms at follow-up, supporting the idea that early cortisol intervention can modulate the long-term psychological impact of traumatic experiences.
    3. Summary: Hydrocortisone has shown promise in reducing PTSD symptoms when administered during or soon after traumatic experiences, particularly in ICU patients or survivors of trauma. Its role appears to be in modulating the stress response and memory consolidation processes.

    Propranolol:

    Propranolol, a beta-blocker, is primarily used to treat cardiovascular conditions but has been studied for its effects on memory reconsolidation and emotional arousal, both of which are implicated in the development of PTSD.

    1. Mechanism: Propranolol reduces adrenergic activity by blocking beta-adrenergic receptors, potentially interfering with the emotional enhancement of traumatic memories, thus reducing their consolidation.
    2. RCT Evidence:
      • Pitman et al. (2002) conducted a double-blind, placebo-controlled trial in which trauma victims (e.g., car accident survivors) were given propranolol or placebo within a few hours of the event. At follow-up, patients who received propranolol had reduced PTSD symptoms compared to those given placebo, though the results were not statistically significant.
      • Brunet et al. (2008) performed a study on individuals with PTSD, where propranolol was administered before memory reactivation (i.e., recalling the traumatic event). The group that received propranolol showed reduced physiological responses to trauma reminders and decreased emotional impact, suggesting that propranolol may weaken the reconsolidation of traumatic memories.
      • Stein et al. (2007) did not find a significant reduction in PTSD incidence when propranolol was administered following trauma. This led to mixed conclusions regarding its preventive efficacy.
    3. Summary: The evidence for propranolol is more mixed. While some studies suggest it may reduce PTSD symptoms by weakening emotional memory consolidation, other trials have not demonstrated a significant reduction in PTSD development.

    Conclusion:

    • Hydrocortisone has more consistent evidence supporting its role in preventing PTSD, particularly when administered soon after trauma.
    • Propranolol shows mixed results, with some evidence suggesting it may reduce emotional memory consolidation and PTSD symptoms, though its effectiveness in preventing PTSD development is less conclusive.

    Both treatments hold potential, but more research is needed to establish their routine use in PTSD prevention.

  • Unlocking Relief: Can Prazosin Power Up Depression Treatment?

    Unlocking Relief: Can Prazosin Power Up Depression Treatment?

    The evidence for the use of prazosin in major depressive disorder (MDD) comes mainly from smaller studies or trials focusing on its off-label use, as prazosin is primarily an alpha-1 adrenergic antagonist used to treat hypertension and PTSD-related nightmares.

    Clinical Rationale

    The theoretical rationale for prazosin in MDD is based on its ability to block alpha-1 adrenergic receptors, which may help reduce the hyperactivity of the norepinephrine system—a pathway implicated in stress and depression.

    Randomized Controlled Trials (RCTs)

    RCT evidence for prazosin in treating MDD is limited compared to other antidepressants, but a few studies have explored its potential benefits:

    1. Prazosin as Adjunctive Treatment for MDD (2009):
      A small pilot RCT assessed prazosin as an add-on therapy for MDD in patients who were already on standard antidepressants. The results showed modest improvements in depressive symptoms when prazosin was combined with SSRIs or SNRIs, particularly in patients with high anxiety or sleep disturbances.
    2. Prazosin for PTSD and MDD Comorbidity:
      Some RCTs conducted in patients with PTSD (a condition often comorbid with MDD) showed improvements in both PTSD and depressive symptoms. For example, a trial published in 2015 demonstrated that prazosin led to a significant reduction in depressive symptoms in veterans with PTSD and depression. While the trial primarily focused on PTSD, the secondary outcomes regarding depression were positive.
    3. Prazosin and Treatment-Resistant Depression (TRD):
      Some trials have explored prazosin’s efficacy in treatment-resistant forms of depression, hypothesizing that its ability to reduce stress-related symptoms could augment antidepressant efficacy. However, these trials have generally been small, and results have been inconsistent or not statistically significant in terms of primary depressive outcomes.

    Limitations

    • Sample Sizes: Most studies are small and underpowered.
    • Population: Most studies have focused on patients with PTSD, rather than pure MDD.
    • Adjunctive Use: Prazosin has mostly been tested as an adjunctive treatment, not as monotherapy for depression.

    While prazosin has shown some promise in improving depressive symptoms, particularly related to sleep disturbances and anxiety, larger RCTs specifically targeting MDD are needed to establish its efficacy.

  • Cyproheptadine in Anorexia: Appetite Booster or Waste of Time

    Cyproheptadine in Anorexia: Appetite Booster or Waste of Time

    Over the past few posts, I’ve been using real cases from my practice to highlight essential teaching points in managing complex conditions. Anorexia nervosa, one of the most severe and high-mortality disorders I encounter, demands a multifaceted approach, especially in critical cases. Recently, I had to explore every possible option to support a particularly challenging case, including cyproheptadine—a medication with potential benefits in anorexia. I decided to dive deeper into the evidence supporting its use. At the end of this post, I’ll share my own experience with cyproheptadine in this case and whether it made a difference in the outcome

    Cyproheptadine has been studied in the treatment of anorexia, particularly anorexia nervosa, due to its appetite-stimulating and antihistaminic properties. Some early randomized controlled trials (RCTs) suggested it might have benefits, especially for anorexia nervosa with certain subtypes, but the evidence has been mixed, and it’s not widely recommended in current guidelines.

    1. Weight Gain: Cyproheptadine has been shown in some RCTs to help promote weight gain in individuals with anorexia nervosa, particularly in those with a restricting type of the disorder. However, results have not been consistent across studies, with some trials finding minimal or no effect on weight gain.
    2. Symptom Relief: Cyproheptadine may help reduce anxiety and obsessive thoughts related to food, as its antihistaminic and mild sedative effects can have a calming influence. However, this has not been strongly confirmed across all trials.
    3. Limitations and Side Effects: The mixed evidence may relate to differences in study designs, anorexia subtypes studied, and dosages used. Side effects, such as sedation, have also limited its use, especially in outpatient settings where these effects might interfere with daily functioning.

    Overall, while some RCTs have shown cyproheptadine might help with weight gain and symptom relief in anorexia, particularly in non-binging types, the evidence remains inconclusive. In my personal practice with the medication, I saw limited if any benefit by adding this medication to current standard of treatment. We are often looking for solutions to complex difficult to treat conditions such as anorexia, but the benefits here seem to be limitted both from the research and clinical perspective. 

  • Can Amantadine Tame Tardive Dyskinesia? Exploring the Evidence and Potential Benefits

    Can Amantadine Tame Tardive Dyskinesia? Exploring the Evidence and Potential Benefits

    In my practice, I see many patients who have been on high doses of antipsychotics for extended periods, particularly first-generation antipsychotics, which carry a higher risk of developing tardive dyskinesia (TD). While two FDA-approved treatments for TD exist, their high cost and limited availability can make access challenging in community mental health settings. This has led me to explore alternative treatments like amantadine. Like many of you, I wanted to understand the evidence supporting its use, so let’s take a closer look at what the research says about amantadine as a treatment option for TD.

    The evidence for the use of amantadine in treating tardive dyskinesia (TD) has been explored in several small randomized controlled trials (RCTs), though it remains limited compared to other treatments.

    1. Efficacy of Amantadine: Some studies suggest that amantadine, an NMDA receptor antagonist, may offer mild to moderate improvement in TD symptoms by modulating dopaminergic pathways. For instance, an early RCT (2007) tested amantadine in schizophrenia patients with TD and reported some improvements in abnormal involuntary movements compared to placebo. However, the sample size was small, and results were modest.
    2. Comparative Effectiveness: Few trials directly compare amantadine to other TD treatments like VMAT-2 inhibitors (e.g., valbenazine, deutetrabenazine), which are the preferred treatment options due to stronger RCT evidence. Amantadine’s effects may be less pronounced, though some patients have reported partial symptom relief, especially when TD is not severe.
    3. Safety Profile: In RCTs, amantadine is generally well-tolerated in TD patients, with few serious side effects. However, common side effects include dizziness, insomnia, and gastrointestinal issues, which may limit its use in certain patients, particularly those with cognitive or movement comorbidities.

    Overall, while RCTs support some benefit of amantadine in TD, the effect size is generally moderate. VMAT-2 inhibitors are preferred based on stronger, more consistent RCT data, although amantadine may still be considered for patients who cannot tolerate or do not respond to these primary therapies.

  • The Silent Crisis: Physician Suicide in the United States

    The Silent Crisis: Physician Suicide in the United States

    I saw these magnets today on the refrigerator located in the physicians lounge and it seemed like a good reminder 

    In the U.S., an estimated 300-400 physicians die by suicide each year, a staggering rate far higher than that of the general population. This crisis, largely unspoken in healthcare settings, underscores the immense pressures physicians face daily. The high expectations, long hours, emotional exhaustion, and the stigma around seeking mental health support create a dangerous environment where burnout can quickly spiral into severe mental health struggles.

    Physicians are trained to endure, often putting others’ health before their own. But the costs of “pushing through” take a toll. Many feel they cannot safely reach out for help without risking their careers due to institutional stigma around mental health treatment. This cycle of isolation and suppressed emotion can lead to tragic outcomes.

    Organizations are beginning to address this issue by implementing wellness programs, peer support systems, and confidential mental health resources, but more systemic changes are needed. Reducing the stigma around mental health support, reforming punitive policies, and fostering a culture of openness in medicine could be life-saving.

    Physician suicide affects us all—it robs the healthcare system of dedicated professionals and leaves profound impacts on patients, families, and communities. It’s time to break the silence and actively support those who care for us.

  • Breaking the Cycle: Effective Strategies to Prevent Self-Injurious Behavior (SIB)

    Breaking the Cycle: Effective Strategies to Prevent Self-Injurious Behavior (SIB)

    This post comes from another real-world case that I frequently encounter in clinical practice. Self-injurious behavior (SIB) is common in the inpatient care setting and the strategies to prevent it are mostly behavioral. Many patients and families are also looking for pharmacological options. Here are some of the more common options and recommendations for treating SIB.

    Behavioral Interventions

    1. Functional Behavior Analysis (FBA): Start with an FBA to understand why the self-injury is occurring (e.g., to gain attention, avoid demands, or self-soothe). This guides intervention planning.
    2. Positive Reinforcement and Skill Building: Reinforce alternative, adaptive behaviors that fulfill the same needs as self-injury, such as communication skills (e.g., teaching to request attention) or self-soothing techniques.
    3. Cognitive Behavioral Therapy (CBT): For individuals able to engage in talk therapy, CBT can address underlying thoughts and emotions driving SIB, such as distress intolerance, perfectionism, or negative self-beliefs.
    4. Dialectical Behavior Therapy (DBT): DBT is particularly effective for reducing SIB, especially in borderline personality disorder. It combines emotional regulation, mindfulness, and distress tolerance skills.
    5. Environmental Modifications: Minimizing triggers in the individual’s environment can help reduce occurrences. This might include changes in routines, avoiding overstimulation, or modifying demands.
    6. Applied Behavior Analysis (ABA): Techniques from ABA, like differential reinforcement of other behaviors (DRO) or non-contingent reinforcement (NCR), can reduce self-injury by decreasing its functional value.

    Pharmacological Interventions

    1. SSRIs (Selective Serotonin Reuptake Inhibitors): Useful if self-injury is driven by anxiety, depression, or obsessive-compulsive tendencies. SSRIs can help stabilize mood and reduce anxiety, lessening the need for SIB.
    2. Antipsychotics: Atypical antipsychotics, such as risperidone or aripiprazole, are sometimes effective, particularly in autism spectrum disorders or severe intellectual disabilities. However, weigh these benefits against side effects, especially for long-term use.
    3. Mood Stabilizers: Medications like lithium, lamotrigine, or valproate can help regulate mood fluctuations that contribute to SIB. Lithium, in particular, has shown effectiveness in reducing aggression and impulsivity.
    4. Naltrexone: This opioid antagonist can be effective in cases where SIB is hypothesized to release endogenous opioids, providing a calming effect.
    5. Beta-blockers (e.g., propranolol): In cases of high impulsivity or aggression linked to SIB, beta-blockers can reduce physiological arousal, lessening the drive for self-injury.
    6. Clonidine or Guanfacine: These medications, which target the noradrenergic system, can help reduce impulsivity and aggression in patients with ADHD or autism, indirectly lowering self-injury.

    Choosing the best approach depends on the individual’s specific triggers, co-occurring conditions, and underlying motivations for SIB. Integrating both behavioral and medication interventions, while monitoring closely for effectiveness and side effects, often yields the best outcomes.

  • Brighten Your Mood: Light Therapy to Combat Daylight Savings Blues!

    Brighten Your Mood: Light Therapy to Combat Daylight Savings Blues!

    With daylight savings time quickly approaching a summary of the randomized controlled trial evidence for light therapy in seasonal affective disorder (SAD), particularly in relation to daylight savings time seems appropriate this week. 

    Efficacy of Light Therapy for SAD

    Several randomized controlled trials have demonstrated the efficacy of light therapy for treating seasonal affective disorder:

    A meta-analysis of randomized controlled trials found that bright light treatment was associated with a significant reduction in depression symptom severity in SAD, with an effect size of 0.84 (95% CI: 0.60 to 1.08)

    Another meta-analysis revealed that dawn simulation light therapy was also effective for SAD, with an effect size of 0.73 (95% CI: 0.37 to 1.08)

    One study found that exposure to bright light (10,000 lux) for as little as 20-40 minutes could lead to significant improvements in mood scores in SAD patients

    Timing and Duration of Light Therapy

    Light therapy is typically administered daily for at least several weeks during the fall and winter months

    One study found that 40 minutes of exposure to 10,000 lux light resulted in greater improvement than 20 minutes, but was not significantly different from 60 minutes of exposure

    The rate of mood improvement was steepest during the first 20 minutes of light exposure

    Mechanisms and Considerations

    The efficacy of light therapy is thought to be related to its effects on circadian rhythms and neurotransmitters like serotonin

    Light boxes used for therapy should provide 10,000 lux of light and have screens that filter out UV rays

    Light therapy is generally recommended to be used within the first hour of waking up in the morning

    Limitations of Current Evidence 

    Many studies on light therapy for SAD have not used rigorous study designs

    There is limited research specifically examining the effects of light therapy in relation to daylight savings time changes.

    More long-term follow-up studies are needed to assess the safety and potential side effects of light therapy

    While the evidence supports the efficacy of light therapy for SAD, there is a need for more rigorous, large-scale randomized controlled trials to further establish its effectiveness, optimal timing, and duration, particularly in relation to daylight savings time changes. The current evidence suggests that light therapy can be an effective treatment option for SAD, with effects comparable to antidepressant medications

    Resources: 

    https://psychiatryonline.org/doi/10.1176/appi.ajp.162.4.656

    https://pmc.ncbi.nlm.nih.gov/articles/PMC2913518

    https://www.mayoclinic.org/diseases-conditions/seasonal-affective-disorder/in-depth/seasonal-affective-disorder-treatment/art-20048298

  • ADHD and Cannabis Use Disorder: Key Facts You Shouldn’t Ignore

    ADHD and Cannabis Use Disorder: Key Facts You Shouldn’t Ignore

    1. Prevalence and Patterns of Use

    People with ADHD have been shown to use cannabis at higher rates than those without ADHD. Studies indicate that adolescents and adults with ADHD are more likely to use cannabis, and they may start using it at a younger age. This may be due to self-medication attempts, as people with ADHD often report using cannabis to help with symptoms like impulsivity, anxiety, and sleep difficulties which seems like a bad idea to me but lets look at the reasons.

    2. Cannabis as a Self-Medication Attempt

    Some people with ADHD use cannabis in an attempt to self-manage their symptoms. Anecdotally, users report feeling more focused, relaxed, and less anxious, though the scientific evidence on cannabis’s effectiveness for ADHD symptom management is not robust. Studies show that while some ADHD symptoms like restlessness might feel alleviated short-term, long-term outcomes often do not show sustained benefit, and impairment can increase over time.

    3. Impact on ADHD Symptoms

    Research on cannabis’s effect on ADHD symptoms is mixed:

    • Impulsivity and Attention: Cannabis can impair attention, memory, and executive functioning, which are already areas of struggle for individuals with ADHD. Heavy cannabis use is associated with poorer performance on tasks measuring these cognitive domains.
    • Cognitive Function: Longitudinal studies have shown that chronic cannabis use can worsen cognitive functions over time, especially if use begins in adolescence. These cognitive impacts may compound ADHD-related deficits.
    • Motivation and Goal-Directed Behavior: Cannabis can affect motivation and goal-directed behavior, which can exacerbate some ADHD symptoms, particularly in individuals who already struggle with organization and task completion.

    4. ADHD as a Risk Factor for Cannabis Use Disorder

    Studies suggest that people with ADHD may be more prone to developing cannabis use disorder (CUD) compared to the general population. Traits like impulsivity and sensation-seeking, common in ADHD, may increase vulnerability to addiction. Additionally, the reinforcing effects of cannabis (e.g., reduction in perceived anxiety) may lead to increased use and dependency in those with ADHD.

    5. Genetic and Neurobiological Factors

    There is some evidence suggesting that the overlap between cannabis use and ADHD may have a genetic or neurobiological basis:

    • Genetic Overlap: Studies have found that genes linked to ADHD, particularly those affecting dopamine function, are also implicated in substance use disorders, including cannabis use disorder.
    • Endocannabinoid System: ADHD and cannabis use affect dopamine and endocannabinoid systems. Some research posits that dysregulation in these systems might underlie both the propensity for ADHD and substance use, but this remains an area for further research.

    6. Cannabis and Medication Interactions

    For those with ADHD taking stimulant medications, cannabis use can interfere with treatment. THC, the psychoactive component of cannabis, can interact with medications like methylphenidate or amphetamine-based treatments, potentially reducing their effectiveness or exacerbating side effects like anxiety and heart palpitations.

    7. Longitudinal and Population Studies

    Long-term studies generally show that early and heavy cannabis use is associated with worse outcomes for individuals with ADHD. These include lower academic achievement, increased rates of unemployment, and higher incidences of mental health issues, especially when cannabis use starts in adolescence.

    Summary

    While some people with ADHD report short-term symptom relief with cannabis, research shows that heavy, frequent use tends to worsen cognitive deficits associated with ADHD over time. Additionally, ADHD may predispose individuals to higher rates of cannabis use and a greater risk of developing cannabis use disorder. While cannabis might seem beneficial for symptom relief in the short term, its long-term use is generally not supported as an effective management strategy for ADHD.

  • Split or Stick? The Real Impact of Dividing Clozapine Doses

    Split or Stick? The Real Impact of Dividing Clozapine Doses

    This post comes from a recent discussion I had with my resident about the utility of splitting clozapine doses in a recent case we had.

    The evidence on splitting clozapine into multiple daily doses primarily stems from clinical observations and smaller studies rather than extensive, randomized controlled trials (RCTs). Since clozapine has a unique pharmacodynamic and pharmacokinetic profile, standardizing an RCT on dose splitting has been challenging.

    1. Clozapine’s Half-Life and Steady-State Concentration: Clozapine has a long half-life (averaging about 12 hours), meaning steady-state concentrations can be reached without strict multiple dosing. Many patients maintain stable blood levels with once-daily dosing, especially at lower doses.
    2. Dose Splitting and Side Effects: Some smaller studies and clinical observations suggest that splitting doses can help reduce peak plasma levels of clozapine, which can be associated with side effects like sedation, hypotension, and dizziness. In these cases, a split dosing regimen may improve tolerability, particularly in patients who experience significant sedation or orthostatic hypotension with a single daily dose.
    3. Metabolic Side Effects and Compliance: In cases where metabolic side effects are of concern, or in patients who may not tolerate high single doses well, dividing doses could help with tolerability, potentially improving compliance and minimizing adverse effects like sedation or metabolic impact.
    4. Seizure Risk: High plasma peaks with a single large dose may theoretically increase the risk of seizures, especially in patients on higher doses of clozapine. Dividing doses is sometimes recommended as a preventive measure to maintain a more consistent blood level, although robust RCT data supporting this specific benefit is lacking.

    While RCT evidence specifically on clozapine dose-splitting remains limited, clinical judgment, patient tolerance, and monitoring of therapeutic blood levels play essential roles in tailoring dose regimens.

  • Raising the Bar: Should Buprenorphine Doses Be Higher to Combat Opioid Use Disorder?

    Raising the Bar: Should Buprenorphine Doses Be Higher to Combat Opioid Use Disorder?

    The study “Association of Daily Doses of Buprenorphine With Urgent Health Care Utilization” explored how different buprenorphine doses affect emergency department (ED) and inpatient service use among individuals with opioid use disorder (OUD).

    1. Higher Doses Associated with Fewer Acute Care Visits: Patients receiving higher doses of buprenorphine (above 16 mg/day) had a longer time to ED or inpatient visits compared to those on lower doses (8-16 mg/day). Those on doses over 24 mg saw a significant reduction in the need for urgent care, particularly related to behavioral health crises.
    2. Implications for Fentanyl Users: The findings are particularly relevant for those using synthetic opioids like fentanyl, which often require higher doses of buprenorphine to manage withdrawal symptoms effectively. These higher doses may reduce acute care needs and improve overall treatment outcomes.
    3. Policy Considerations: The study highlights potential barriers, such as restrictive state laws or insurance limitations, that may prevent patients from accessing higher buprenorphine doses, which could limit effective treatment.

    These results suggest that modifying buprenorphine dosing guidelines could be beneficial, especially as the opioid crisis evolves with the prevalence of fentanyl​

    Link to article: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2824049