Medication Side Effects: Doctor my mouth is a little dry

Regular Dental Care and Oral Hygiene

Dry mouth is another common side effect from psychiatric medication. Patients on psychiatric medication often have poor dental care and poor dental outcomes. There is increased incidence of dental caries and oral ulcers in this population. This patient population is also three times more likely to lose all their teeth. Let that sink in for a moment. Now some of this is related to not following the recommended dental hygiene guidelines such as regular cleanings at least every 6-months. Thus, this is the first step in the process. Ensure the patient first has a dentist, and second be sure they are making regular 6-month appointments, and if they have issues with dental health, they should be going for cleanings as often as every 3 months. Oral hygiene is the foundation for the remainder of the interventions.

Gum, Candy, and Pilocarpine

Most patients are told to carry a bottle of water around and take frequent sips throughout the day. This does not work. It provides temporary relief, and does not address the underlying issue. You can educate the patient about drinking more water while eating which can help facilitate the swallowing process especially when dry mouth is an issue. Carrying a cup of ice can be helpful but is not convenient. What I prefer is the use of sugarless gum or candy which can be easily carried and chewed as needed. Studies have demonstrated that xylitol containing gum can reduce the levels of Mutans streptococci and lactobacilli in saliva and plaque. This has the potential to reduce the incidence of dental caries, and is an inexpensive option for most patients. I will also recommend as a second line using a mouth wash for dry mouth such as Biotene. If these interventions are not effective a medication to stimulate saliva production such as pilocarpine. In many cases pilocarpine eye drops which act locally is a better option than a medication that acts systemically. 

Final Words

Dry mouth is a common side effect patent’s experience but may not always bring to the clinician’s attention. There are interventions to treat this side effect that range from simple interventions like xylitol containing gum to pharmacological interventions such as pilocarpine eye drops. Most patients will experience relief with the above treatments. This highlights the importance of asking about specific side effects so they can be treated early and prevent long term Complications such as tooth loss. 

Reducing Anxiety and Altering Patterns of Avoidance

Thinking Style in Anxious Patients 

  • There is a heightened level of attention to potential threats in the environment 
  • Example: A women with fear of airplanes has to fly across the country for work, she believes the plane is likely to crash despite the low risk of this actually occurring.

Predominant thinking patterns in Anxiety 

  1. Fears of harm and danger 
  2. Increased attention towards potential threats 
  3. Overestimation of the risk of situations 
  4. Automatic thoughts associated with danger, risk, uncontrollability, incapacity
  5. Underestimates of ability to cope with fearful situation 
  6. Misinterpretation of bodily stimuli 

Avoidance

  • The emotional and physical response to the feared object or situation is so severe that the person will do anything to avoid it. 
  • Because the avoidance behavior is rewarded with emotional relief, the behavior is more likely to occur when the person is faced with similar circumstances. 
  • Example: A person with anxiety is invited to a party and decides to make up an excuse not to go and the anxiety is relieved. Each time the person is faced with a similar situation they are likely to act the same way. 

CBT Model for Anxiety

  1. Unrealistic fear of objects or situations 
  2. A pattern of avoidance reinforces the belief that I cannot deal with the feared object or situation 
  3. The pattern of avoidance must be broken to overcome the anxiety. 

Behavioral Treatments

  • There are two general methods of behavior treatment for anxiety 
  • Reciprocal inhibition: A process of reducing emotional arousal by helping the person experience a positive or healthy emotion in place of the unhealthy one. (deep breathing, relaxation techniques) 
  • Exposure: expose yourself to the stressful situation, fear will occur but cannot be sustained indefinitely and the person will begin to adapt to the situation. 

Assessment of symptoms, triggers, and coping strategies

  1. What is the event that triggers the anxiety? 
  2. What are the underlying automatic thoughts, cognitive errors, and schema involved in the overreaction to the feared stimulus?
  3. What is the emotional and psychological response? 
  4. Habitual behaviors such as avoidance?

Cognitive Errors

  • Cognitive errors have been found to occur more often in people with depression and anxiety.
  • There are 6 main categories of cognitive errors 
  • Selective abstraction: A conclusion is drawn after looking at only a small amount of information. Other contradictory information is screened out to confirm the persons biased view of the situation.
  • Arbitrary inference: A conclusion is reached in the face of contradictory evidence or lack of evidence
  • Overgeneralization: a conclusion is made about one or more isolated incidents and then extended illogically to cover broad areas of functioning.
  • Magnification or minimization: The significance of an attribute event or sensation is exaggerated or minimized.
  • Personalization: external events are related to oneself when there is little or no evidence for doing so.
  • Absolutistic thinking: judgments about oneself, others or personal experiences are placed into one of two categories: All good or All bad

Techniques:

  1. Relaxation training: reducing muscle tension induces a state of relaxation and often results in reduced anxiety
  • Rate the level of anxiety and muscle tension on a scale of 0 to 100, with 0 being no tension and 100 being max tension 
  • Try making a fist and squeezing to a level of 100, then release it to a level of 0. Try doing so with the other hand. Notice that we have voluntary control over how much tension we feel. 
  • Starting with the legs tense and release each muscle group working your way up to the head. (I prefer to do this laying down) 
  • Try to keep positive mental images in your mind while doing this. Example: picture your tension and worries melting away like ice when left out in the sun. 
  • Try doing this daily for 1 week and record how you feel before and after a session.

2. Thought stopping: Stop negative thoughts and replace them with positive adaptive thoughts. 

  • Recognize: that a dysfunctional thought pattern is active 
  • Give self-instructions to interrupt the thought pattern:  Shift attention away from the anxiety provoking thought. (STOP! Or Don’t go there!) 
  • Consider guided images: try to imagine doing something enjoyable, playing a game, watching a sport, going on vacation. This can be combined with muscle relaxation  

3. Distraction: Develop several positive scenes that you can go to when anxious. Examples include walking in a nice park, going to your favorite restaurant, and spending time with friends/family 

4. Decatastrophizing: examine the evidenceto see that the likelihood of adverse outcomes is much less than we estimate

  • Estimate the likelihood: of the event occurring. Rate it on a scale of 0 to 100% 
  • Evaluate the evidence: for and against the event occurring 
  • Review the evidence list: now re-estimate the risk of the event occurring after going through the evidence 
  • Create an action plan: brainstorm strategies to reduce the likelihood of catastrophic occurring. Write down actions that you could take to prevent the feared outcome. 
  • Develop a plan for coping: if the event should occur. 
  • Reassess: compare the original rating to the new rating 
  • Debrief: What was good about working through a catastrophic event in this manner?

5. Deep Breathing

  • Aim for 30-60 breaths, 1-2 cycles
  • Start in the sitting position, hands on la or knees 
  • Take 10 breathes in through the nose and out through the mouth 
  • Take 10 breaths in through the nose and out through the nose 
  • Take 10 breaths in through the nose and hold for 5-10 seconds, then release out through the mouth 

6. Exposure: systematically or all at once (flooding) exposing yourself to the feared object or situation. This is the most important part of CBT for anxiety. Systematic desensitization: graded exposure, starting with less anxiety provoking situations 

  • Be specific: details matter, “stop being afraid to go to parties” is not specific “go to my neighbor’s house party for 20 minutes and talk to one person” 
  • Rate each step on a scale of 0 to 100 depending on how much anxiety you expect to occur 
  • Develop at least 8-12 scenarios that go from lowest to highest anxiety 
  • Work with the therapist to select to order of steps for graded exposure therapy 
  • Two types: imaginal and real-world exposure, depending on the case both may be used (good for OCD and PTSD)  

Medication Side Effects: Doctor I’m Gaining Weight!

One of the biggest challenges we face in the field of psychiatry is medication adherence. A large portion of the people fail to get better either because they do not start the medication, or do not take it as prescribed. One of the most common reason cited by patients for stopping medication is weight gain. In this article I will detail the approach I take to weight management for patients on psychiatric medications. 

Initial Visit: 

Weight management is a discussion that should happen between the patient and clinician at the first meeting. It’s important to use primary prevention (preventing the onset of weight gain) if possible. We always obtain some objective measures such as height, weight, and calculate the BMI on the initial visit and subsequent visits. Additional tests that may be ordered include HBA1C, fasting blood glucose, and lipid profile. This is where I will take the opportunity to discuss the importance of diet and exercise. For people with little diet or exercise experience I will keep the information very basic. The discussion will center around eliminating processed foods, calorie containing beverages, increasing fruit and vegetable intake, and making good choices when shopping at the food store. I have several handouts with food choices on them that help guide the patient when making food choices at the grocery store. I also recommend patient’s keep a food diary or track their food intake on a mobile app such as my fitness pal. This will help us to understand more about the patient’s eating habits and identify potential areas for improvement. I will build on diet interventions and monitor progress with the food diary or app at each visit. I do not recommend a specific diet, as it’s far more important for the patient to pick something they can be consistent with, and there are multiple ways to achieve weight management goals. At this time the closest diet we have that I’m comfortable recommending is the Mediterranean diet. There is some good evidence that the Mediterranean diet can have an antidepressant effect which is an added bonus.

Exercise

Exercise is the next area to address. I like to ask some screening questions about what type of physical activity the patient engages in, and how much experience they have with fitness/athletics. I will then ask them to track their exercise over the subsequent weeks prior to returning for follow up visit. On the initial visit I will recommend they begin a basic walking program of at least 30 minutes per day preferably seven days per week. This is a simple thing to incorporate on a daily basis, and does not require any special equipment or gym membership. We can improve on this routine and incorporate resistance training on a case by case basis. 

Medication Choice

The next step in the process is to make a medication choice that limits the potential for weight gain. Most psychiatric medications cause weight gain. This is an unavoidable fact. Avoiding the use of medications with the highest propensity of weight gain including Clozapine, Olanzapine, and Mirtazapine is good planning on the physician’s part. It’s important to note that it’s not always possible to avoid these medications. Medications such as Aripiprazole which are considered to be weight neutral, from clinical experience are not weight neutral at all. It’s important for the clinician to make good choices if weight gain is a potential issue that will interfere with treatment.

Medication For Weight Management

My last line of defense against weight gain which often comes too late is medication management. I like to start with Metformin extended release 500 mg daily after the largest meal. This is to test the patient’s tolerance for the medication. The goal is to titrate to 2000 mg/day in divided doses. A B12 level should be checked once per year as Metformin has been known to reduce levels. There is evidence in the literature from a Meta-analysis of all RCTs supporting the use of Metformin for antipsychotic induced weight gain. The important thing to remember is to start the medication at the earliest signs of weight gain, or even before the onset of weight gain in high risk patients. The patients most likely to benefit are those who are younger, more recently started on antipsychotics, overweight but nor obese, and those that had rapid weight gain. 

The second medication I will talk about is Topiramate There is evidence from RCTs to support the use of Topiramate for antipsychotic induced weight gain. There is greater weight loss with Topiramate over placebo, with a mean decrease of 2.8 kg. The effective dose for the medication is 100 to 200 mg/day depending on the patient’s tolerance. Getting to an effective dose can often take some time with this medication.

Final Points

Weight management discussions begin day one when medications are going to be used. Prevention is the first line option with lifestyle modification including diet and exercise. Medication choice also plays a big role. When initiating medication being mindful of the propensity for weight gain, and using medications that are weight neutral if possible, can help. If these measures fail, there are a few options backed by research evidence which can be used but I believe lifestyle modification is the best option. 

Choose Your Words Wisely: How We Talk About Addiction Matters

An important discussion we need to have is about the impact of language on stigma in addiction treatment. Language is powerful and labels are sometimes lifelong sentences. As physicians we can choose the language we use when talking with patients and about patients. How can we start to reduce this stigma by replacing harmful language?

  1. Replace the words drug addictdrug abuser, with words like patient with opioid use disorder 
  2. Replace Opioid abuse or dependence with opioid use disorder
  3. Replace problem with disease or illness 
  4. Replace dirty urine with positive or negative urine test 
  5. Replace Relapse with return to use
  6. Replace being clean with remission
  7. Replace Medication assisted therapy with opioid agonist treatment or medication for opioid use disorder

Language is powerful and can influence the perception of addiction and treatment. There have been several advocacy campaigns to change the way we talk about addiction. Friendly reminder to choose your words carefully, it may make a significant difference in peoples lives. 

Help, I think I’m a Narcissist

Introduction

It seems like everywhere I look there’s a video or article with titles such as “how to tell if you’re a narcissist” or “is your significant other a narcissist.” This got me thinking about narcissistic personality disorder (NPD), and why everyone thinks they or someone they know has this disorder. 

Brief Review of NPD Criteria from DSM-5 (5 out of 9 required) 

-Grandiose sense of self-importance 

-Preoccupied with fantasies of unlimited power, success, beauty etc. 

-Believes they are special and unique 

-Requires excessive admiration 

-Has a sense of entitlement (unreasonable expectations) 

– Interpersonally exploitative 

-Lacks empathy 

-Often envious of others or believes others are envious of them 

-Shows arrogant, haughty behaviors and attitudes 

Distinction Between a Disorder, and being a Jerk 

There is an important distinction between having NPD and having narcissistic traits. In diagnosing NPD there is a long list in DSM-5 of which the person must have 5 out 9 criteria to qualify for the diagnosis. These criteria will be present in all circumstances and relationships. Most importantly it must cause impairment in function and a subjective sense of distress. If the person meets these criteria, and it’s working for them in their life, they would not be diagnosed with NPD. You need to have the functional impairment, that is what makes it a disorder. Although these people may not have a disorder, it still does not make them a pleasure to be around. There can still be relationship difficulties both professionally and on a personal level.

Common Types of Narcissism 

The classic grandiose narcissist, this is the kind of person who cannot stop bragging about what they have, and what they have done. They tend to enjoy showing off symbols of status such as new cars or even attractive partners. They do things based on what will get them the most admiration and recognition from others rather than personal values. These types are encountered on a regular basis, you may know people like this in your personal life. 

There is a classic example of the highly successful professional who will stop at nothing to achieve their goals even if it’s at the expense of others. So naturally one place you may encounter these individuals is in the workplace. These types will exploit other people, cheat, work the system, whatever they can do to get ahead. They are usually successful and superficially charming. This pattern is less commonly encountered in daily life.

Oregon First to Legalize Psilocybin for Mental Health Treatment

On Tuesday Oregon became the first state to legalize the psychedelic prodrug found in magic mushrooms. Measure 109 will give legal access to psilocybin for mental health treatment in supervised settings. 

Having followed the research on psilocybin at Center for Psychedelic & Consciousness Research, I am aware of the growing body of research on this topic. Most of the results presented seem to indicate significant benefit with limited side effects. The research I reviewed involves the use of psilocybin for the treatment of substance use disorder. However, I am aware of positive results in the treatment of post-traumatic stress disorder and to enhance the effects of psychotherapy. I am a believer that we need to look at all potential options for the treatment of psychiatric disorders. We know that our current medications only solve some of the problem’s patients are facing. Chronic disorders like substance use and depression remain major clinical challenges. 

As a psychiatrist I’m conflicted about the decision to start offering this treatment even in supervised settings. Like Cannabis, we are only in the beginning stages of studying these drugs as medication. As a physician you remain a scientist first, and as a scientist you want to give the research time to develop. In the United States cannabis remains federally illegal (schedule I). This means funding for research is difficult to obtain. The same is true for psilocybin. We need increased ability to study these drugs as medications and determine the true risks and benefits. There are many anecdotal accounts of the benefits of both these drugs, but I do not believe this is enough to potentially risk your health on. 

I believe research will elicit positive benefits for both cannabis and psilocybin. However, I urge caution when considering these options as potential treatment for mental health disorders. 

Election Anxiety Solutions

Anxiety is a part of life; we all experience it. The amount of anxiety a person experiences is to some degree related to how important a particular outcome is to that person. It seems like everything these days is high stakes and anxiety provoking. There is a global pandemic that continues to create chaos around the world, economic uncertainty, gender and racial inequality, and now a presidential election.

People are more anxious than ever about this presidential election. According to a recent article by the American Psychological Association 68% of U.S. adults say the 2020 U.S. presidential election is a significant source of stress. This is compared to the 2016 election where 52% of U.S. adults found the election stressful. It might just be a symptom of the times, but it remains a significant concern. If you are having election anxiety here are some simple ways to reduce stress and anxiety during this election cycle. 

  1. Make sure you are getting enough sleep. Set a regular sleep time and wake time. Make sure the room you sleep in is as conducive to sleep as possible (e.g. dark room with no ambient light). Limit the bed to sleep and sex only, do not play games on your phone or read in bed. If you can’t sleep get out of the bed and do a mildly strenuous activity. A good example is a crossword puzzle, then come back to bed when you feel tired. If you are not sleeping well it can cause problems in other areas of life such as mood and cognitive function. 
  2. Get outside or stay inside whichever you prefer, but make sure to move. Exercise is a great way to cope with stress and anxiety. There are countless free guided exercise routines on sites like YouTube that require little or no equipment to perform. If you do not like that option, take a walk in your favorite park, take a bike ride, or go for a hike on your favorite trail. 
  3. Limit your consumption of news throughout the day. Set aside one or two times per day to check the news and see what is going on with the election. Resist the urge to continually check in and get play by play updates. This simple, but difficult to follow advice will save you a lot of stress and anxiety. 
  4. Avoid talking to people in your life about the election who are unable to keep their emotions under control while discussing the topic. You should have a good idea of who these people are in your life. This will save you a lot of stress and anxiety by simply choosing to talk about other topics with those individuals.
  5. The last thing I recommend for people who want an activity they can perform to reduce stress is a thought journal . This can be as simple as a piece of paper that you record the thoughts on. There are printable versions of this online. I will provide a link to one such example here. This is a common technique used in cognitive behavioral therapy (CBT) all the time.

What Can We Do to Help Prevent Alzheimer’s disease (AD)

Introduction

The other day I had a conversation with a friend, and the topic of Alzheimer’s disease (AD) came up. My friend’s opinion was basically why would I want to know I have a disease that results in steady decline in function, and lacks any disease modifying treatments? This is in large part true, there have been multiple clinical trials of both symptomatic and disease modifying drugs that failed to produce adequate results. However, this is a very limitted view and neglects the benefits of focusing on modifiable risk factors and primary prevention. We know approximately 1/3rd of AD cases are due to modifiable risk factors, and the implementation of lifestyle modification early may prevent or delay the onset of AD. 

Modifiable Risk Factors

Common modifiable risk factors for AD include hypertension, hyperlipidemia, diabetes, obesity and smoking. Management of these risk factors as early as possible may offer a preventative approach for AD. Equally important are lifestyle modifications such as physical exercise, diet, mediation/mindfulness, and social activity.

Physical Activity

Physical inactivity has a significant influence on the development of AD. Twenty-one percent of AD cases are attributable to physical inactivity. There is a significant number of studies in the literature that indicate physical activity is neuroprotective. We know one of the areas in the brain affected by physical activity is the hippocampus which is involved in memory. Exercise leads to increased neurogenesis and neuroplasticity in the hippocampus. Other benefits of exercise on the brain include increased blood flow, modulation of inflammatory markers, and increased brain-derived neurotrophic factor (BDNF). The exact definition of adequate exercise varies in the literature. Any activity that is sufficient to increase heart rate and can be sustained for 30-60 minutes is my definition. A basic example would be brisk walking for 30-60 minutes. Physical activity two times a week beginning in middle age is associated with reduced risk of AD. Aerobic exercise is associated with additional cognitive benefits including improved processing speed, attention, and memory in adults with mild cognitive impairment. This recommendation is especially important for ApoE4 carriers, as exercise is associated with reduced amyloid deposits. 

Physical activity should be a recommendation for all patients without major health concerns preventing physical activity. The earlier in life a patient begins an exercise routine the better. Some of these studies have looked specifically at starting exercise routines in middle age, but there is no reason to wait. The physical and cognitive benefits of exercise are beneficial regardless of age. It’s much easier to begin training when you are young and healthy. If you build healthy lifestyle habits earlier in life, they are likely to last as you age. Guidelines for regular exercise can be found on the American Heart Association or American College of Sports Medicine websites. 

Meditation

Meditation or mindfulness is a topic that is beginning to get more attention in the medical literature. Chronic stress is believed to effect brain structures involved in memory and may contribute to AD. Psychological stress increases oxidative stress and telomere shortening which could contribute to the neuronal loss seen in AD. Meditation has emerged as a possible way to reduce the stress associated with daily life. The techniques of mindfulness involve directing one’s attention to the present moment to reduce the stress associated with constant thinking and worrying. Randomized controlled trials (RCTs) have shown significant improvements in overall well-being and attention. Improved executive function and reduced inflammatory processes implicated in AD. Additional research and larger RCTs are needed to improve the evidence base. Given the data we currently have there is no reason to not begin mindfulness practices. The techniques are relatively simple and can be learned from a variety of sources. If you are looking for low cost options for learning mindfulness, YouTube has a variety of guided mediations available. I personally like Headspace for beginners because it provides a solid foundation, has a variety of meditation courses, and allows you to track your progress. There is a fee for access to all the courses, but the first 10 sessions are free. Whichever route you choose, spending 10-15 minutes per day practicing mindfulness will lead to a happier and healthier brain. 

Diet

A great deal of research has been conducted over the last several years on the role of diet with respect to cognition. People with high calorie diets, specifically those high in fat are at higher risk for AD. Traditional western diets high in processed carbohydrates, simple sugars, and saturated fatty acids can impact the hippocampus and memory. When Japan transitioned to western diet the incidence of AD increased. Lower calorie diets with lower saturated fat content are linked to lower oxidative stress, decreased Beta amyloid burden, and decreased inflammation. One diet with proven benefits for preventing AD is the Mediterranean diet. This diet is rich in fruits, vegetables, whole grains, olive oil, and fish. There is moderate intake of low-fat dairy products and low intake of red meat, saturated fats, and sugar. Most of the data supporting the reduce risk of AD with this diet comes from epidemiological studies. Studies have shown combining this diet with exercise further reduces the risk of AD. The Mediterranean diet is associated with better cognitive function and reduced cognitive decline. This is one specific example, but the basic principles can be applied without the need to adhere to one specific named diet. 

Some specific foods you may want to add to your diet to prevent AD include fresh berries which have the highest amounts of antioxidants among the fruits. They are also low in calories and work well in diets where weight loss is a goal. Green leafy vegetables and tomatoes have the highest nutritional value when it comes to brain health amongst the vegetables. Foods high in omega-3 fatty acids are considered to be helpful in supporting brain function. The omega-3 fatty acid most important in brain function is docosahexaenoic acid (DHA), which is mostly found in fish. The anti-inflammatory and antioxidant properties of DHA are thought to be responsible for its role in preventing AD. Patients with diagnosed AD are known to have low levels of DHA. Omega-3 fatty acids recommendations from the American Heart association for adults is to eat fish rich in omega-3s two or more times per week. If using a supplement 1-3 grams per day is an adequate dose. Over 3 grams per day, you should consult with your doctor before moving above 3 grams per day. 

Finally, curcumin which is derived from turmeric has anti-inflammatory, antioxidant, and anti-amyloid properties. There is low bioavailability of the curcumin lead to mixed results in the initial trials. A new more bioavailable form called Theracumin demonstrated positive results in a randomized double-blind placebo-controlled study on memory, attention, and amyloid plaques in older adults without dementia. 

Conclusion

While there is no guarantee that lifestyle modification alone will prevent AD, there are some promising studies indicating it plays a role in the development of this disorder. Most of these interventions are things patients can implement in their lives immediately. They will not only improve cognitive function and lower the risk of developing AD, but it will improve and potential reverse other diseases of lifestyle. 

Complementary Alternative Medicine (CAM) in Psychiatry

This is one of the most popular topics patients ask about. Often psychiatry gets a bad reputation for prescribing medication without addressing lifestyle and “natural” options for the treatment of psychiatric illness.

A 2007 National Health Interview Survey (NHIS) reported 4 out of 10 American adults and 1 out of 9 children used CAM. The most commonly cited reasons for using CAM are depression, insomnia, anxiety, and chronic pain. Typically, integrative care involves the use of traditional medical therapy with appropriate evidence-based CAM. This is not always the case, and often times you will find many people who are not licensed medical doctors offering advice on CAM. What I hope to accomplish in this post is to introduce some of the CAM options that are evidence based for depression.

While the use of CAM is widespread, randomized controlled trials for specific CAM interventions have issues with their study design. They are usually conducted for short durations, and have a small number of participants. Despite these limitations, many CAM research studies report positive benefits for depression. Likewise finding high quality products with appropriate dose of active ingredient can also be a challenge. There are many companies and not all of them are reputable. 

It’s unlikely that CAM will be enough to treat severe cases of major depressive disorder alone. For mild to moderate cases of depression, it may be effective based on the evidence detailed below.

Below are the options I would consider CAM for primary treatment of depression. In the next post I will talk about adjunctive treatment for people who have had response to antidepressants but not remission of symptoms.

Hypericum Perforatum (St. John’s Wort) 

St. John’s Wort (SJW) is a medical herb with antidepressant activity. The exact mechanism by which this herb improves mood is not fully understood. SJW is known to inhibit monoamine reuptake, and down regulate monoamine receptors in the brain. In 2005 Linde et.al conducted a meta-analysis of 37 randomized double-blind placebo-controlled trials (RCT) which demonstrated superiority of SJW to placebo. It’s important to note SJW was equivalent to antidepressant treatment for mild cases and inferior for severe depression. In 2017 Ng QX et al. conducted a meta-analysis which found a similar result. They looked at 27 clinical trials and a total of 3808 patients, comparing the use of SJW with SSRIs for the treatment of depression. They concluded that for mild to moderate depression, SJW had comparable efficacy and safety when compared to SSRIs.

How does SJW stack up against traditional SSRIs? Fava et al. conducted a randomized double-blind trial of SJW, fluoxetine and placebo for major depressive disorder. SJW was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. Sarris et al. analyzed date from a 26-week RCT that studied SJW vs. Sertraline and placebo for major depressive disorder. The comparison between all treatments was not significant. Both SJW and sertraline were therapeutically effective, but they could not say one was superior to the other. 

Although SJW is effective for the treatment of depression, it’s not my favorite choice. SJW is a known inducer of the cytochrome P450 enzymes. SJW can increase clearance of medications including antiretrovirals, oral contraceptives, benzodiazepines, digoxin, and phenobarbital. When SJW is combined with other antidepressant medication there is increased risk of serotonin syndrome. 

S-Adenosyl-Methionine (SAMe)

SAMe is an amino acid that is distributed widely throughout the brain and is the major methyl donor required for the synthesis of monoamine neurotransmitters. It’s available in the United States over the counter. Studies indicate that SAMe levels may be reduced in patients with MDD.

Several reviews of the literature on SAMe and depression have been conducted. Most of the reviews conclude that SAMe is generally effective for the treatment of depression. However, more carefully designed higher quality studies need to be conducted. A meta-analysis that looked at 28 studies concluded that SAMe was superior to placebo for the treatment of depression, and it was found to be statistically significant. Again, this study did not find a difference between SAMe and traditional antidepressant treatment. Another review of 11 studies concluded that SAMe resulted in a reduction in depressive symptoms and was superior to placebo. One study showed benefits of SAMe as an adjunctive therapy to SSRIs in patients who were non-responders.

SAMe does have some associated side effects including mild gastrointestinal (GI) problems and insomnia. There is risk of inducing a manic episode in patients with bipolar disorder, and SAMe should be avoided in this population. Patients taking medication for Parkinson’s disease may have reduced efficacy of the medication when taken in conjunction with SAMe. Thus, we should avoid SAMe in this population as well. 

References

  1. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;2008(4):CD000448. Published 2008 Oct 8. doi:10.1002/14651858.CD000448.pub3
  2. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. J Affect Disord. 2017;210:211-221. doi:10.1016/j.jad.2016.12.048
  3. Fava M, Alpert J, Nierenberg AA, et al. A Double-blind, randomized trial of St John’s wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005;25(5):441-447. doi:10.1097/01.jcp.0000178416.60426.29
  4. Sarris J, Fava M, Schweitzer I, Mischoulon D. St John’s wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry. 2012;45(7):275-278. doi:10.1055/s-0032-1306348
  5. Galizia I, Oldani L, Macritchie K, et al. S-adenosyl methionine (SAMe) for depression in adults. Cochrane Database Syst Rev. 2016;10(10):CD011286. Published 2016 Oct 10. doi:10.1002/14651858.CD011286.pub2
  6. Sharma A, Gerbarg P, Bottiglieri T, et al. S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. J Clin Psychiatry. 2017;78(6):e656-e667. doi:10.4088/JCP.16r11113

Depression Etiology: Brain-Derived Neurotrophic Factor (BDNF)

Brain-Derived Neurotrophic Factor (BDNF) is a substance in the brain that promotes neuronal growth. It’s also involved in neuroplasticity in the developing brain. There is increasing interest in the role of BDNF in depression for several reasons.

We know that various brain structures are decreased in size in patients with major depressive disorder. Specific areas include the anterior cingulate, prefrontal cortex, and amygdala all of which are implicated in depression. Decreased serum levels of BDNF have been found in patients with depression and may be in part responsible for these changes.

Mutations to the BDNF gene have been associated with major depressive disorder (MDD). Antidepressant medications can increase BDNF, and in part may explain the effects of these medications.

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