- The only FDA approved use of trazodone is for depression. However, this medication is rarely prescribed for this purpose. The higher dose requirements and lower affinity for the serotonin transporter allows the side effect profile to make the medication intolerable for most patients.
- The most common way it’s used is as an adjunctive therapy for sleep disturbances secondary to depression.
- The mechanism of action is blockade of serotonin 2A receptors and blockade of the serotonin reuptake pump.
- Dosing: To take advantage of the sedating properties you want to use a lower dose. A dose of 25-150 mg/night is appropriate. For depression the dose must be much higher anywhere from 150-600 mg/day
- For depression start with 150 mg/day in divided doses (short half-life) and increase every 3-4 days by 50 mg/day as needed to a target dose of 400 mg/day. For insomnia start with 25-50 mg/night and increase as tolerated to a target dose of 50-150 mg/night. That same target range of 50-150 mg/day can be used if trazodone is being added as an adjunct therapy for depression.
- It’s very important to start low and go slow when increasing the dose. Patients can have carryover sedation, ataxia, and intoxicated like feeling if titrated too rapidly.
- Do not stop the medication prematurely. In difficult to treat patients’ higher doses may be required 150-300 mg or up to 600 mg in some cases.
- It’s ideal to try and limit dosing to once nightly at bedtime to avoid daytime sedation
- Notable Side effects: Nausea, vomiting, constipation, dry mouth, dizziness, sedation, fatigue, headaches, life threatening side effects include priapism (1 in 8,000 men), seizures, activation of suicidal ideation in patients under 24 years of age.
- The onset of therapeutic actions for insomnia should be immediate once an adequate dose is reached. There is no evidence of tolerance, abuse potential, or withdrawal.
- Therapeutic action for depression is delayed by 2-4 weeks if it’s not working by 6-8 weeks consider a dosage increase or switch depending on dosage reached
- Trazodone offers a nonaddictive option for insomnia treatment and can be used as an adjunct for depression treatment. It’s less likely than other antidepressants to cause sexual dysfunction. It may be less likely to precipitate hypomania or mania and may have some benefit for treating agitation and aggression associated with dementia.
- Quetiapine offers some benefits over other dopamine blocking medications. It has a much lower risk for EPS and a broad spectrum of effects. The main limitations are weight gain, sedation, and orthostasis. The extended-release formulation offers a once nightly dosing that can reduce daytime sedation.
- It has a number of FDA approved indications including use in schizophrenia, bipolar disorder, bipolar depression, and major depression as an adjunct
- It’s mechanism of action is blocking dopamine D2 receptors which targets positive symptoms of psychosis and serotonin 2A receptors which enhance dopamine release in certain regions of the brain reducing motor side effects and possibly improving cognitive side effects. It’s effects on depression and bipolar depression may be related to 5HT1A partial agonist activity, norepinephrine reuptake blockade, and 5HT2C and 5HT7 antagonist properties.
- Clinically quetiapine is often underdosed and stopped or switched before an adequate trial is completed. Higher doses generally achieve greater response for manic or psychotic symptoms.
- For schizophrenia start with 25 mg BID or 300 mg XR QHS. Target doses 400-800 mg/day
- For bipolar start with 50 mg BID or 300 XR QHS. With a target dose of 400-800 mg daily for mania and 300 mg/day for depression (studies indicate that 600 mg was not better for depression than 300 mg)
- For depression start at 50-100 mg/day in divided doses with a target of 150-300 mg/day (data indicates that 150 mg and 300 mg do equally well so either dose is appropriate depending on patient response)
- You can increase the dose 50-100 mg/day every 1-4 days to a target dose
- The max daily dose in adults is 800 mg/day, occasionally patients may require 800-1,200 mg/day for psychosis or mania
- Monitoring is similar to other dopamine blocking medications, specifically fasting blood glucose and lipid profile, BMI, blood pressure
- Side effects include sedation, hypotension, dry mouth, dizziness, constipation, weight gain and fatigue. Watch for orthostatic hypotension at high doses or with rapid titration. There is essentially no motor side effects or prolactin elevation.
- For XR formulations do not crush or chew them, if a patient has been off the medication for more than 1 week you want to restart as if initial therapy. Quetiapine has some abuse potential reported in the literature particularly in incarcerated populations
- In the initial studies with beagle dogs cataracts developed but human studies have not shown this association
- The gut microbiome consists mostly of bacteria and that is largely the portion of the microbiome we are focusing on (fungi and viruses exist but their function is largely unknown)
- Communication pathways exist between the microbiota-gut-and brain.
- Multiple mechanisms exist that allow gut microbiota to signal to the brain and control physiological processes.
- These include release of gut peptides from enteroendocrine cells which activate receptors of the immune system and vagus terminals in the gut.
- Studies indicate that these bacteria can manufacture and secrete essential neurochemicals including serotonin, dopamine, NE, GABA, and acetylcholine
- Depression and anxiety have been linked to a less well diversified gut microbiome.
- What can help diversify the gut microbiome? Diet, processed food, sugar, saturated fats, and red meat. Medication can also alter the gut microbiome, a good example is oral antibiotics used to treat an acute infection, sleep, exercise. Sounds a lot like a healthy lifestyle will get you the microbiome you need for optimal mental health.
- However, if you want a treatment there have been several studies that looked at fecal transplant to treat psychiatric disorders. Fecal transplants are much easier these days and now there is a capsule version that you take orally. There is not enough data to recommend this as a practical treatment and if the patient goes back to eating a poor diet, sleeping poorly, not exercising then the gut microbiome will revert after the transplant.
- What are the practical things you can do? Stop eating processed food, sugar, and red meat. Increase your fiber intake and select a diet like the Mediterranean diet or a plant based whole food diet that will provide those prebiotics. You could supplement with a probiotic but most of what you need can be had from a good diet alone and I think it’s far better to change the diet then to try using supplements to treat a poor diet. Fermented products like kimchi, kombucha and sauerkraut are good sources of live bacteria.
- If you choose to take a probiotic make sure it’s a quality, 3rd party tested product.
- Increase aerobic activity, I think if you goal is overall general health and you have limitted time, I think aerobic activity is a better bang for your buck.
- The way I believe you get and keep a healthy gut microbiome is through lifestyle modification. Improving your diet, exercise, and sleep is a good place to start. If you want to supplement with food products like kimchi or kombucha, go for it. I do not believe there is enough evidence to support a probiotic supplement for psychiatric disorders at this point, but if you want to spend $30 or more per month on a product if it’s a quality one that’s fine. Remember you cannot supplement away a bad diet.
How to use Pramipexole
- Selective D3 agonist thought to be related to hedonic drive.
- FDA approved for Parkinson’s disease and restless leg syndrome
- 5 randomized controlled trials indicating effectiveness in depression as monotherapy or adjunctive therapy and in bipolar disorder as adjunctive therapy with a mood stabilizer
- Side effects; nausea, hypotension, and fatigue, titrate slowly and give the dose at night
- Start with 0.125-0.25 mg QHS and rise by 0.25 mg every 5-7 days towards a target dose of 0.75-2 mg QHS
- Watch for hedonistic homeostatic dysregulation (HDD) including pathological gambling and shopping
I get a lot of questions that go something like this, I’ve been on X, Y, Z medications and nothing seems to help. It seems that what most are asking about is what is the algorithm for treating depression and when does it become treatment resistant. This video will provide a look at what treatment resistant depression is and provides a 5-stage strategy to medication selection.
- Schizoaffective disorder has features of both schizophrenia and mood disorders (bipolar and depression).
- Two sub types: depressed type and bipolar type
- The diagnosis can get complicated because primary mood disorders can have psychotic features (MMD with psychotic features or bipolar disorder with psychotic features), patients with schizophrenia can have mood symptom most commonly depression.
- The lifetime prevalence is less than 1%, the most recent data indicates 0.3% but I would say there is a range between 0.5-0.8%
- More women have the depressed type greater than 2:1 ratio
- Equal number of men and women have the bipolar type
- The cause of schizoaffective disorder is unknown. It may be a type of schizophrenia, a type of mood disorder, but most likely it’s a spectrum that combines all these things.
- Schizoaffective disorder has a better prognosis than schizophrenia but a worse prognosis than primary mood disorders.
- Patients are said to have a nondeteriorating course and respond better to lithium than patients with schizophrenia.
- Schizoaffective disorder combines the features of both schizophrenia and affective mood disorders.
- If the mood is primarily manic, it’s called schizoaffective disorder bipolar type
- If the mood is primarily depressed it’s called depressed type
- The mood component should be present for the majority > 50% of the total illness
- You must have a two-week period where psychotic symptoms and are present in the absence of mood symptoms
- Treatment will depend on the predominant symptoms. If the patient has more mania than a mood stabilizer will be used (e.g., lithium)
- For psychotic symptoms, dopamine blocking medications will be used (e.g., risperidone)
- For depressive symptoms serotonin reuptake inhibitors will be used (e.g., sertraline)
Highlights From the Video
Immediate release the medication is released immediately and results is quick onset and a peak blood level. This type of formulation is generally less expensive and may be advantageous in some cases. For example, if you are using quetiapine at night in part for its sedating effects, I will use immediate release because I want a rapid effect. The same with methylphenidate or bupropion.
The problem is this formulation requires twice a day or even three times per day dosing and results in more peaks and troughs. In general, for medications that are being used for maintenance you want consistent blood levels and not peaks and troughs.
With IR formulations, there can be more side effects and addictive potential. We believe it’s the rapid rise in blood levels of the medication that cause side effects and with medications like amphetamines for ADHD it’s the rapid rise in medication levels that can result in euphoria and thus addictive potential.
Extended release does not change the active ingredient in the medication, rather it provides a different delivery mechanism that slows the release of medication over an extended period of time. This has the opposite effect on blood levels when compared to IR. There will be less peaks and troughs and more sustained blood levels of medication. The advantage is once daily dosing and potentially fewer side effects for the pervious mentioned reasons.
The downside is these medications tend to cost more money and some have argued when initiating these medications, a patient who has an adverse reaction will have symptoms longer with XR. Although clinically I’m not sure this is true and will generally use extended release if possible for maintenance medications.
Amidst the abundance of coverage of the 2020 presidential election mixed with an evolving pandemic, here is a news story you may have missed: it’s 2020 and guns are more popular than ever in the US. According to data from Small Arms Analytics to date, Americans have purchased nearly 17 million guns in 2020. This is more than any previous year on record. Handgun sales increased by 81% and long-gun sales increased by 51%. We saw a similar trend in 2016 when 16.6 million guns were sold. This was driven by increased rhetoric calling for strict gun control laws in the wake of several mass shootings.
As psychiatrists and concerned citizens, this data is alarming. We know that the presence of a gun in the home alone increases the risk of suicide. Specifically, owning a handgun is associated with a dramatic increase in suicide risk. Men who owned handguns were eight times more likely to die by self-inflicted gunshot wound. Women who owned handguns were 35 times more likely to kill themselves with a gun. Access to guns in the home is such a concern for depressed patients that it’s a part of every psychiatric evaluation. Suicide is often an impulsive act, and many of those who survive a suicide attempt regret their actions. Guns permit people to be dangerously impulsive. Lethality of means determines whether a person will survive a suicide attempt. In the United States, where more civilians’ own firearms than any other country, our most lethal means are guns. Suicide attempt by firearm will most likely result in death: an irrevocable and permanent result of the combination of an impulsive decision and a gun.
So, what is this about? Is there an increased interest in hunting that some of us missed? The plain answer is no. Most guns purchased in the US are not intended for hunting; instead, people are purchasing guns for “protection.” The increase in gun sales comes at a point in history of great political and social unrest. Maybe it is unsurprising that people feel an urge to protect themselves and their families. Fear is at an all-time high.
You know what else is at an all-time high? Isolation, loneliness, anxiety and depression. The most well-adjusted people are struggling in 2020. Depressed moods can progress to clinical depression which may include suicidal thoughts as part of the diagnostic criteria. Now, we have a country full of depressed people buying guns. In the mental health field, we are scared. You should be too. The financial, political, and public health uncertainties of today’s world form a perfect substrate for depression, fear, and impulsivity. Adding a gun is not the way to fix it.
We know that gun access provides a substantial risk for suicide. It remains important that we educate our patients about the risk of gun ownership. This is especially important for patients who have a history of depression or other psychiatric disorders. All this could be a potentially dangerous combination of psychopathology, and access to lethal means.
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
- Fears of harm and danger
- Increased attention towards potential threats
- Overestimation of the risk of situations
- Automatic thoughts associated with danger, risk, uncontrollability, incapacity
- Underestimates of ability to cope with fearful situation
- Misinterpretation of bodily stimuli
- 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
- Unrealistic fear of objects or situations
- A pattern of avoidance reinforces the belief that I cannot deal with the feared object or situation
- The pattern of avoidance must be broken to overcome the anxiety.
- 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
- What is the event that triggers the anxiety?
- What are the underlying automatic thoughts, cognitive errors, and schema involved in the overreaction to the feared stimulus?
- What is the emotional and psychological response?
- Habitual behaviors such as avoidance?
- 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
- 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)
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.