How to Change Your Mind: The Current State of Psychiatry and Psychedelics

There is no hotter topic in the world of psychiatry than the reemergence of psychedelics as therapeutic tools for the treatment of mental illness. When esketamine was approved by the FDA in March of 2019 it opened the doors for medications like MDMA, psilocybin, and mescaline as possible therapeutic agents. 

I’m excited about these new options for therapy but I also want to make sure the science backs up the personal experiences of individuals who use these medicines in uncontrolled settings. 

Introduction:

The psychedelic era was a time of social, musical, and artistic change influenced by the use of psychedelic drugs that occurred between the mid-1960s and mid-1970s. Although this era lasted for some time it largely fell out of favor for legal reasons and wasn’t a topic in modern psychiatric training until just recently. It seems like overnight there are New York times articles, Netflix documentaries, and evening news coverage about psychedelics.

What’s the story are we ready to prescribe everyone psilocybin and MDMA as a form of mental health treatment? 

History of Hallucinogens in Medicine

For over 5 millennia humans have been attempting to alter their state of consciousness. Some have argued it goes even further back to primate ancestors who consumed large quantities of ripe fermented fruit to alter their state of consciousness (drunken monkey hypothesis). I’m not sure how correct this theory is but it’s safe to say psychedelics have been around for a long time. 

In 1943 Albert Hofmann a chemist by training, invented LSD by accident. He started the research in 1938 and announced that he sampled the chemical in 1943. Not only did he synthesize it, but he was getting high on his own supply. In 1957 this same chemist isolated psilocybin from the hallucinogenic mushrooms.

In the 1940’s LSD was marketed as a drug to assist psychotherapy, the so-called drug assisted psychotherapy which is making a comeback today. Unfortunately, of the 1000 studies published looking at psychedelics as a model for psychosis and as therapy were small and uncontrolled. 

In the 1970’s most of these medicines were placed into schedule I status making it exceedingly difficult to study the medicines further for therapeutic effects in a controlled setting. A Randomized controlled trial is considered by many to be the highest standard of scientific evidence. 

Classes of Hallucinogens 

For years people thought of psychedelics as LSD or psilocybin, the term now includes other medicines. The term psychedelic is derived from two Greek words meaning mind manifesting. Essentially psychedelic and hallucinogen are being used interchangeably these days but do have separate meanings.

Classic Hallucinogens 

-Tryptamines: psilocybin, LSD, and DMT 

-Phenethylamines: Mescaline 

Non-Classic Hallucinogens 

-3,4-methylenedioxymethamphetamine (MDMA)

-Dissociative Anesthetics: Ketamine, PCP, Dextromethorphan 

Therapeutic Targets for Psychedelic Use

Disorders Under Investigation: 

-Depression 

-Anxiety

-PTSD

-OCD

-Cancer related stress and psychological issues 

-Addiction 

-Smoking cessation 

-Sexual dysfunction 

-headaches 

-inflammatory disorders 

Maybe the best studied area is in end of life and palliative care settings. 

Mechanism of Action

-The primary mechanism of action is 5-HT2A receptor stimulation 

-5-HT2A is the most abundant serotonin receptor in the central nervous system and cortex of the brain. 

-Stimulating the 5-HT2A receptors will increase the release of glutamate in the cortex 

-Stimulation of 5-HT2A receptors in the visual cortex can lead to visual hallucinations. Stimulation in the ventral tegmental area can produce a situation like that of schizophrenia with delusions and hallucinations. 

-Most atypical antipsychotics bind to and block 5-HT2A receptors and would mitigate the effects of psychedelics 

Neurobiology

People often make comments like we don’t know how much serotonin is enough, then conclude that medications do work or the therapies we are using are invalid. That’s because they are thinking about mental illness and these medications too simply. Most psychiatrists do not believe in or talk about the chemical imbalance theory of treating mental illness. We think about mental illness and problems with neural circuits, nodes, and networks. What medications including the psychedelics achieve is an alteration in the connectivity of these networks and the ability to form new connections. 

We have a default mode network which is famously active when a person is not focused on the outside world and the brain is just daydreaming. What psychedelics do is decrease brain connectivity in this default mode network followed by the establishment of new connections. 

Hypothetically this rewiring of the brain allows for the replacement of faulty connections resulting in mental illness and the formation of new healthy connections through psychotherapy provided during treatment. This may be why the antidepressant effects last far beyond other interventions with less frequent dosing. 

There are identifiable changes in network connectivity that coincide with subjective improvement. 

The Mystical Experience: Is Tripping Required for a Therapeutic Effect

-There is a mystical experience questionnaire that has been validated and used in these studies. It seems that the more profound the mystical experience the better the treatment effect subjectively 

-While the spiritual experience many individuals have while taking these medicines is profound and meaningful to the individual, we are not sure that having a “trip” is required to produce a therapeutic effect. 

Side Effects of Psychedelic Use 

While some may claim there are no adverse effects from plant-based medicine that is not true. 

Things like increased blood pressure, berating rate, and body temperature have been reported. 

-Loss of appetite, dry mouth, sleep disturbance, uncoordinated movements, panic, paranoia, psychosis, and bizarre behaviors 

Long-Term Effects: 

Persistent Psychosis: A series of continuing mental problems including 

-visual disturbances

-disorganized thinking

-paranoia

-mood changes 

Hallucinogen Persisting Perception Disorder (HPPD) 

-Recurrences of certain drug experiences such as hallucinations or visual disturbances 

-These experiences often happen without warning and may occur within days of last use or even years after taking the drug 

-These experiences can be mistaken for neurological disorders such as strokes or brain tumors. 

Conclusion

At this time what we can say about the current state of psychedelics in psychiatry is they are under investigation. We do not know yet if they are safe and effective for treatment of mental illness on a mass scale. We have some encouraging evidence but there is an absence of large randomized controlled trials proving efficacy and safety. Psychedelics are not ready for clinical practice and should not be recommended as a treatment for mental illness until the proper studies have been conducted. 

When Serotonin Goes Bad

Many medications that work as so-called antidepressants will increase serotonin by blocking the reuptake pump. In general, we think of increased serotonin in a patient with depression as a good thing, but what happens when increased serotonin goes bad? 

That is what we are here to talk about today, what happen when there is too much serotonin in the central nervous system?

Being prescribed too many serotonergic medications can result in Serotonin Syndrome which can range from mild to severe and is potentially fatal. It can present with muscle rigidity, hyperthermia, and altered mental status. 

When someone has increased muscle tone, and elevated temperature with no other explanation, it’s time to look at their medication list. Medications can increase serotonin release, block reuptake, or directly activate serotonin receptors. Common examples include linezolid, Fentanyl, and dextromethorphan.

Watching from drug interactions like CYP 450 inhibitors can increase medication levels resulting in serotonin syndrome. Whenever a new medication is prescribed consider doing a drug interaction check to make sure the new medication doesn’t inhibit a critical cytochrome. 

Mild forms of serotonin syndrome may cause diarrhea or tremor where the more severe cases are more likely to result from a drug overdose. 

Key Features of Serotonin Syndrome: 

  • Patient is on one or more serotonergic drugs 
  • The onset of symptoms is abrupt usually within 24 hours and symptoms peak rapidly 
  • There is increased tone in the legs more than the arms, tremor and hyperreflexia are present 
  • Vital signs show hypertension, hyperthermia, tachycardia, and tachypnea 
  • Labs can show increased creatinine kinase 

What is Clonus: 

  • Involuntary, rhythmic muscle contractions. 
  • It occurs more in the lower extremities 
  • To induce clonus, you flex the patient’s foot upward until there is rhythmic beating of the foot and ankle. If the beating continues beyond a couple of beats, it’s abnormal 

Treatment: 

  • For mild cases discontinue serotonergic medications and check for drug interactions. Use external cooling measures and start benzodiazepines. 
  • For moderate cases where the vital signs are worse and there is spontaneous clonus or agitation: use the same measures as above, increase the frequency and dose of the benzodiazepine, and start cyproheptadine 12 mg followed by 2 mg every 2 hours until improvement is seen followed by 8 mg every 6 hours for maintenance. Cyproheptadine is an anticholinergic, antihistamine, and anti-serotonergic medication 
  • In severe cases, where delirium develops and there is a failure to respond to other measures, admission to the ICU and the use of paralytics with intubation and ventilation are required 

 

The Neurobiology of Appetite

Metabolic set point 

People alter the quantity and frequency of food consumption daily and yet the brain seems to have a regulatory process that allows people to maintain a relatively stable body weight. 

Isn’t that crazy? 

Anyone who has ever tried to diet knows all too well about this metabolic set point. There are staggeringly low rates of success with diet programs. A systematic review of studies published between 1931 and 1999 found that only 15% of patients achieved dietary success after 5 years. Most people who diet will slowly return to their preexisting weight within 1 year.

This metabolic set point appears to be controlled by our genetics. There is a strong correlation between the body mass of biological parents and adoptees in adoption-based studies. In the case of weight, genetics has far more influence than environmental factors. 

Despite all this obesity rates in the United States as well as other developed countries continues to rise, so what gives? 

Our genes have difficulty responding to the modern environment. 3000 years ago, when food sources were scarce, it was advantageous to consume and store as many calories as possible. However, in the modern world where there is no shortage of opportunity to consume calorie dense foods, our genetics are working against us. The weight issue is genetic but also influenced by availability of high-calorie delicious food. 

When it comes to weight, energy in (food) must equal energy out (heat and work). The energy out is made up of the resting metabolic rate (calories burned when the body is stationary) and physical activity. The brain has a unique mechanism for managing the RMR. When more calories are consumed the RMR increases and when we diet the RMR is turned down. 

To solidify the point, we can look no further than The Biggest Loser competition. Investigators assessed 14 of the 16 contestants before the competition, after completion of the 30-week program, and 6 years after the show. 13 of the 14 study participants regained weight and 4 were heavier than when they started the competition 6 years ago. The real downer was they all burned less calories at rest 6 years after the show ended. Despite exercising more and theoretically being much healthier their RMR decreased. 

What are the important signals used by the body that indicate when to eat and when to stop eating?

Short-Term signels include: 

Glucose: This is the primary nutrient that mediates satiety. Hypoglycemia will stimulate hunger and increase eating, while glucose infusions will decrease food intake. 

Mechanoreceptors in the gut: The physical presence of food in the stomach activates these receptors due to stretching, the vagus nerve transmits signals of gastric stretch to the hindbrain to decrease eating. 

Gut Hormones: The most well understood is cholecystokinin (CCK) which is released by endocrine cells in the small intestine. This will inhibit further food intake by stimulating the vagus nerve and decreasing gastric emptying. People have tried using CCK as a weight loss measure but all it does is decrease the size of meals but increases the frequency of eating thus producing a net zero effect on weight loss.

Ghrelin is the only gut hormone that stimulates hunger. Some suggest that decreased ghrelin produced by the stomach is the reason gastric bypass surgery is effective for weight loss. 

It’s now known that adipose tissue releases a hormone that conveys information about energy stores. Leptin is produced by fat cells and increases or decreases based on the total amount of fat. Leptin is a hormone that tells the body to stop eating. In the case of obesity leptin levels are high and energy expenditure increases while food intake decreases. When someone goes on a diet and fat stores decrease leptin decreases resulting in decreased energy expenditure and increased food intake. 

Two groups of neurons in the arcuate nucleus of the hypothalamus mediate the leptin signal, proopiomelanocortin (POMC) and neuropeptide Y (NPY). POMC stops eating and NPY increases food intake and decreases energy expenditure. In obesity there is increased leptin which inhibits NPY and activates POMC resulting in increased energy expenditure and decreased food intake. The opposite is true for the lean individual. 

Eating and Pleasure

It’s well established that eating can result in pleasure, we have all had this experience after a stressful week a good meal can instantly change our mindset. The pleasure from food is likely an adaptation that enhanced survival when food sources were scarce. Increased dopamine in the nucleus accumbens and release of endogenous opioids appears to be more active when we are eating a meal we enjoy. 

Omega-3 Fatty Acids and Mental Health

Omega-3 fatty acids are reported to help with several physical and mental health conditions. 

They are termed essential because they cannot be produced by the body and must come from the diet. 

In fact, I use 1000 mg of omega-3 fish oil daily as part of my own supplement routine.

How Do Omega-3s Work:

Omega-3’s coat neurons, increase cell membrane fluidity, have neuroprotective properties, and the most well-established mechanism is an anti-inflammatory action. They directly affect arachidonic acid metabolism because they displace arachidonic acid from membranes and compete with it for the enzyme that catalyzes the biosynthesis of thromboxanes, prostaglandins, and leukotrienes involved in the inflammatory process thus reducing the formation of these products. 

Indications For Omega-3 Use In Psychiatry:

In mental health the most well-established use of Omega-3s is for the treatment of depression. It’s been looked at as a primary treatment as well as augmentation. The results aren’t that great when Omega-3s are used as stand-alone therapy. As augmentation they have an effect size of 0.5 to 0.6.

Given our previous talks about inflammation and depression, people with high inflammatory biomarkers may respond better to Omega-3 treatment. 

Omega-3s And Schizophrenia:

Maybe the most interesting data comes from studies of Omega-3 use in schizophrenia. It seems to work best when started early in the illness when the first signs or symptoms appear. There also seems to be a reduction in white matter changes on imaging studies. 

This raised the important question; can we prevent schizophrenia? 

Vienna Study:

There was a study published in nature communications that looked at outcomes in the prevention of psychotic disorders in Vienna. 

They started with 12-week trial with omega-3s which proved to reduce the risk of progression to a psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared to placebo. 

They then completed a long term follow up of the study to show that brief intervention with Omega-3s reduced the risk of progression to a psychotic disorder and psychiatric morbidity. 

A year after the Omega-3 treatment only 5% converted to schizophrenia, compared to 28% in the control arm. Seven years later the rates of conversion to schizophrenia were 10% Vs 40% with most of the patients being retained in the study. 

Side Effects of Using Omega-3:

There are very few risks to adding omega-3 fatty acids to existing psychiatric treatments. Fish burps are a common occurrence and can be mitigated with enteric coated capsules or refrigerating the capsules. Omega-3 can increase bleeding time and require careful monitoring if the person is scheduled for surgery or taking anticoagulants. Keeping doses at 1000 mg/day is advised for this population. 

Sources of Omega-3:

You can use a supplement, or you can consume fish like salmon, herring, or anchovies two times per week to get an adequate dose. 

Ensuring the EPA to DHA ratio is 2:1 (EPA: DHA) or pure EPA is essential when selecting a product. Consumerlabs.com to help ensure the purity and potency of the product is accurate. 

The cost of adding an Omega-3 supplement to your treatment is $8 to $30 per month depending on the specific product. 

There is very little downside to increasing your consumption of Omega-3 fatty acids either from whole food sources or as a high-quality supplement. 

Everything You Need to Know About Trintellix (Vortioxetine)

Introduction:

Vortioxetine is sold under the brand name Trintellix, and Brintellix and it’s approved for use in major depressive disorder. The name was changed to Trintellix in the U.S. due to confusion with Brillinta an anti-platelet medication. It was studied in generalized anxiety disorder (GAD) at lower doses, but the quality of the evidence is poor and does not appear to improve symptoms or quality of life in patients with GAD. 

I want to make a quick point before going into the details about the medication. When I say the effect size is moderate and Vortioxetine does not perform better than other options for depression, I’m not saying in an individual case that it may not outperform other antidepressants that the person has tried in the past. It very well might for that individual. I’m talking about on average in large sample sizes, Vortioxetine does not outperform other medications according to the current literature. It’s also not a go to medication for treatment resistant depression, the literature does not support this either.

The one place Vortioxetine does seem to stand out is cognitive function. Multiple studies have shown this medication to improve cognitive dysfunction associated with depression. It also appears to improve cognitive function in geriatric depression but failed to show any benefit in neurocognitive disorders like Alzheimer’s disease. It was also looked at as a potential treatment for attention deficit hyperactivity disorder (ADHD) but failed to show an adequate benefit in trials. 

Mechanism of Action and Receptor Targets

This medication falls into a class known as serotonin modulators and stimulators. It is thought to work by several different mechanisms:

-Serotonin reuptake inhibitor

-5-HT1A agonist (may diminish sexual side effects) 

-5-HT1B partial agonist 

-5-HT1D, 5-HT3 (may enhance noradrenergic and cholinergic activity that improves cognition while reducing nausea), and 5-HT7 antagonist (pro-cognitive and antidepressant effects) 

The most robust action is on serotonin reuptake and 5-HT3 antagonism, while the other interactions are considered minor. 

Target Affinity Ki (nM)Action 
SERT1.6Inhibition 
NET113Inhibition 
5-HT1A 15Agonist 
5-HT1B33Partial agonist 
5-HT1D 54Antagonist 
5-HT2C180 
5-HT3A3.7Antagonist 
5-HT719Antagonist 

Metabolism

Vortioxetine is metabolized by CYP2D6, 3A4/5, 2C19, 2C9, 2A6, 2C8 and 2B6, the half-life is 66 hours and it’s dosed one time per day. Reduction is dosing may be needed for patients taking strong CYP2D6 inhibitors (e.g. bupropion).

Dosing:

-5-20 mg/day 

-Tablets come as 5 mg, 10 mg, and 20 mg 

-The initial dose for depression is 10 mg which can be increased as needed to a maximum dose of 20 mg daily. 

-For GAD does were kept lower 5-10 mg/day range 

-Can be taken with or without food 

-It can be stopped without a tapper 

Side Effect:

Common side effects include nausea, vomiting, constipation, sexual dysfunction, weight gain is unusual but possible. Nausea and sexual dysfunction were the most common side effects; all other side effects were reported in less than 10% of cases. 

Sexual dysfunction was found in both the plebe group and the treatment arm. The incidence was 14-20% for placebo and 16-34% for those in the treatment arm.

Rare life-threatening side effects include seizures, induction of mania and suicidal ideation. 

Avoid using tramadol as it can increase the risk of seizure, and do not combine with MAOIs as this can result in serotonin syndrome. 

It’s generally not recommended in pregnancy. 

Conclusion

While this medication may be helpful for some individuals there is no evidence to support its use in treatment resistant depression or other disorders outside of the primary indication major depressive disorder. There does seem to be a benefit for patients who have significant cognitive dysfunction as a result of depression and maybe that is where this medication best fits into a treatment plan. The main side effects are nausea and sexual dysfunction which are common with all antidepressant options. You must also consider the cost of the medication in comparison to duloxetine which outperformed Vortioxetine in some clinical trials.

 

Major Depressive Disorder (MDD) With Psychotic Features

This is a diagnosis that I often receive questions about. It can be confusing, how do we know if the person has schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features? 

They all have psychotic symptoms such as delusions and hallucinations.

In this video I’m going to explain how we navigate this diagnostic dilemma. 

For one to be diagnosed with MDD with psychotic features they must meet criteria for major depressive disorder based on the DSM-5TR. 

As a reminder, to meet criteria the person must have 5 out of 9 symptoms within a two-week period and at least one symptom must be either depressed mood or loss of interest

In medical school they teach you the mnemonic SIGECAPS, an interesting fact is this is written the way you would fill out a paper prescription for depression. SIG Energy Capsules which you would give to a person with major depression because of the low energy and loss of interest commonly seen in major depression. 

Anyway…

The other criteria include 

-Weight loss or weight gain 

-Insomnia or hypersomnia 

-Psychomotor agitation or retardation 

-Fatigue or loss of energy 

-Feelings of worthlessness or guilt 

-Poor concentration 

-Recurrent thoughts of death or suicidal ideation 

So, we have a person who meets criteria for MDD, they have 5 out of 9 symptoms for a two-week period. 

We should keep in mind it’s important that the person has also suffered some loss of function in their personal or professional life because of the symptoms. This is what makes it a disorder. 

Now, what if the person also has a loss of reality-based thinking in conjunction with the major depressive episode?

This will include things like delusions and hallucinations. The delusions can be persecutory in nature or paranoid, but other types may occur too. The persecutory delusions are ones where the person feels attacked or victimized by others. They may even believe people are coming into their home to harm them. This usually presents with the patient reporting things being moved in the home or things being out of place. A common paranoid delusion is one where the person believes they are being followed. This usually presents as a car or person the patient keeps seeing, and they cannot believe that it may just be a coincidence, or someone who travels the same route to work every day.

Delusions are fixed false beliefs, and although there may be rational explanations for the things going on around them, this is the patient’s reality, and you must be careful when challenging it. The belief is fixed, and That is why presenting evidence contrary to the belief is not effective.  

The important point here is the psychotic symptoms are only present during the major depressive episode. Treat the depression and the psychotic symptoms resolve. If the psychotic symptoms remain after the major depressive episode is successfully treated, you need to reevaluate the diagnosis.

This is what separates MDD with psychotic features from schizophrenia. 

In bipolar disorder with psychotic features, the psychosis often occurs in the manic phase of the illness and has a grandiose theme associated with it. The patient my for example believe they are a prominent religious figure, or the government is plotting against them. 

We often call the delusions in depressive episodes mood congruent, meaning they are consistent with how the person is feeling. It’s not a far stretch for a person who is severally depressed to feel like people want to harm them. 

Treatment

Treatment is well established and consists of an SSRI or other antidepressant medication in combination with a dopamine blocking medication. The other option is electroconvulsive therapy (ECT) when the person is severally depressed not eating, attending to ADLs, or at risk for suicide. 

Patients should remain on medication for at least 6 months after complete resolution of symptoms. This is very important as relapse has been proven to occur when medication is stopped prior to that time. People can taper off the dopamine blocking medication after 6 months as these tend to have worse side effect profiles. The SSRI should be continued for 1 year at which time you can attempt to taper off or reach a lowest effective dose if symptoms begin to reappear. An index phase of ECT should be completed if that is the treatment of choice which consists of 12 total sessions done either 2 or 3 times per week. 

Malingering In Psychiatry

  • Let’s first define malingering, this is the production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives. 
  • Not all lying involves secondary gain, but ALL malingering does involve secondary gain 
  • Common secondary gains include avoiding military service, avoiding work, financial incentives, avoiding legal actions, and obtaining controlled substances 
  • Feigning mental illness is not the same as malingering because the reason behind the false production of symptoms is not assumed with feigning symptoms. 
  • Factitious disorder is the voluntary production of symptoms, but this is with the goal of assuming the sick role or role of a patient, it’s not done for secondary gain. 

Consider malingering when….

-Rare symptoms are present 

-Improbable symptoms are being reported

-Rare combination of symptoms are present

-Reported Vs observed symptoms are not congruent

Malingered Depression:

-25-30% of patients who claimed major depression in civil litigation were probably malingering

-Pay careful attention to facial expressions 

-Pay careful attention to motor function, psychomotor retardation is an important observable sign

-If appetite changes are reported look for actual objective weight change 

-symptoms opposite of depression 

-blaming others for everything is not the way guilt typically presents in depression, this is externalizing and not taking personal responsibnility

Malingered Psychosis: 

-Often in true psychosis people can describe the voice/s, is it loud, soft, male, female, you have some experience of what you heard. When you ask a malingering patient about a voice, they should have some ability to describe what they are hearing, if not consider malingering.

-If you are suspicious, begin with open ended questions, ask them to describe things in their own words. 

-Genuine AH are in words or sentences, drug Hallucinations usually occur as unformed noises.

-The location of the voice inside the head or outside is no longer a good predictor of malingering 

-Many times the content of voices are derogatory in nature

-Other signs of malingered psychosis include Vague or inaudible auditory hallucinations, AH not associated with delusions (86% of AH have an associated delusion), no strategies to diminish voices 76% of patients have some coping strategy to diminish the voices. They claim that all instructions are obeyed, the hallucinations are visual alone, seeing little people or giant people for example.

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

Most Commonly Prescribed Psychiatric Medications: Trazodone

  • 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. 

Most Commonly Prescribed Psychiatric medications: Seroquel or Quetiapine

  • 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 

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