Attention Deficit Hyperactivity Disorder ADHD: Treatment

-This is one of the only disorders where medication is the first line treatment in children and adolescents.

-There is a 70%-80% response rate to psychostimulants, and medication consistently outperforms behavioral interventions in RCTs.

-For preschool age children, behavioral interventions are first line and medications are considered if there is a poor response to behavioral intervention and functional impairment. 

Psychostimulants 

Methylphenidate (MPH or Ritalin) should be started at 2.5 to 5 mg twice daily (before breakfast and lunch). It can be increased by 2.5 to 5 mg/day reaching an optimal dose of 1 mg/kg/day and a maximum dose of 2 mg/kg/day. 

Side effects include insomnia, decreased appetite, mood disturbance, tics, headaches, GI distress, and rarely psychosis. 

-There are several long-acting preparations including Ritalin XR, Ritalin LA, metadate, Concerta, Daytrana, Focalin XR and several others. The important point about long-acting preparation is they provide a sustained second release with resulting plasma levels lasting 4-12 hours depending on the preparation. 

Amphetamine sulfate (Adderall): should be started at 2.5-5 mg once or twice per day. It can be increased by 5 mg per week with an optimal dose of 0.5-1 mg/kg/day. Dextroamphetamine is twice as potent as amphetamine. The side effect profile is similar to MPH. 

Longer-acting amphetamine preparations include Adderall XR, Dexedrine, Dyanavel XR, and Vyvanse (formulated as a prodrug to reduce the risk of abuse). These will provide coverage for about 12 hours. 

-There is a black box warning for the risk of abuse and dependence. In addition, there is a cardiovascular safety warning regarding the risk of sudden cardiac death in children and adolescents with structural heart defects or other severe cardiac conditions. Patients should be screened for any cardiovascular disorders, family history of sudden cardiac death, and an EKG should be performed. 

Attention Deficit Hyperactivity Disorder (ADHD)

Diagnosis

-ADHD is the most common physiocratic disorder in children. 

-Its prevalence is 5-11% in school-aged children 

-It often presents with a classic triad of inattention, hyperactivity, and impulsivity 

– However, it can present as mixed, or primarily inattentive or hyperactive 

-Symptoms must include at least 6 signs of inattention and/or six signs of hyperactivity/impulsivity for 6 months. 

-For patients 17 years and older on 5 symptoms are required 

Symptoms of inattention include

-failure to pay close attention 

-difficulty sustaining attention on tasks or activities 

-failure to listen when spoken to 

-difficulty organizing tasks 

-avoidance of activities that require mental effort 

-losing things necessary for tasks or activities 

-distractibility and forgetfulness in daily activities 

Symptoms of hyperactivity

-fidgeting with hands or feet 

-inability to sit still 

-running around when not appropriate 

-difficulty engaging quietly in activities 

-feeling on the go or driven by a motor 

-talking excessively 

Symptoms of Impulsivity

-answering questions before they are completely asked 

-having trouble waiting ones turn 

-interrupting others 

The pattern of behavior must be more severe and occur more often than in other children of the same age. The symptoms of the disorder must be present before the age of 12 years. The diagnosis can be made after 12 years of age but there must be evidence of symptoms before the age of 12. The last important point is the symptoms must occur in two different settings (e.g., home and school). 

Many patients may be familiar with screening scales like the Vanderbilt or Conners which can be used to help confirm the diagnosis usually one is completed by the parent the other by a teacher. 

Most Commonly Prescribed Psychiatric Medications: Desvenlafaxine/Pristiq

Desvenlafaxine is the active metabolite O-desmethylvenlafaxine (ODV) of venlafaxine and is formed as a result of CYP450 2D6. It shares many of the same properties as venlafaxine. 

  • It’s FDA approved for Major depressive disorder 
  • Mechanism of action: This medication will boost the neurotransmitters serotonin, norepinephrine, and dopamine. It does so by blocking the serotonin reuptake pump, the norepinephrine reuptake pump, and increases dopamine in the frontal cortex because dopamine is largely inactivated by the norepinephrine reuptake pump in the frontal cortex. 
  • The dosing is a little easier than venlafaxine. You can start with 50 mg/day with a maximum dose of 100 mg/day. In some cases, doses of 400 mg/day have been shown to be effective but there is increased risk for side effects at higher doses. 
  • Desvenlafaxine is more potent at the serotonin transporter but has greater norepinephrine transporter inhibition relative to venlafaxine. This is one advantage along with lower does required to achieve that inhibition. 
  • These tablets should not be broken, crushed, or chewed, it will alter the controlled release.
  • It has some of the same issues as venlafaxine when it comes to withdrawal or discontinuation. It can be difficult to taper off and may require starting fluoxetine prior to tapering. 
  • Blood pressure must be monitored regularly during treatment.
  • Most common side effects include: nausea (most common 12%), dizziness (8%), increased sweating (6%), constipation (5%).
  • Other side effects: decreased appetite, decreased libido, erectile dysfunction, abnormal dreams, tinnitus, vertigo 
  • I’ve had many questions about combining this with mirtazapine. It can be combined with mirtazapine. Trazodone and bupropion are other popular medications to combine with desvenlafaxine if monotherapy does not result in remission. 
  • Desvenlafaxine offers some benefits over venlafaxine including more consistent plasma levels due to lack of metabolism by CYP 2D6, it has more potent action at the norepinephrine transporter than venlafaxine. It may be a better option if you are targeting the norepinephrine system. 

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. 

How to Sleep Better: Prescriptions From Your Psychiatrist

I will talk about sedative and hypnotic medications in future videos, but I want to start a discussion on sleep with sleep hygiene. I recommend all my patients start here and follow this process at least 90% of the time prior to talking about medication. I find most patients are not doing these things and if they are it’s not consistent enough to see a noticeable improvement. 

  1. Stick to a routine by waking up at approximately the same time each day. Do this for seven days, and do not alter the time on weekends. This will help you gradually set your internal clock. You have more control over your wake times than your sleep time as you may not feel tired. Try to avoid taking a nap during the day even on nights where you do not get much sleep.
  2. Avoid all caffeine after 12 PM, the effects of caffeine are long lasting and can interrupt sleep. If you can completely stop caffeine that would be best, but at the very least minimize consumption before 12 PM. 
  3. Try to exercise daily (seven days per week), preferably early in the day and not too close to bedtime. Start with 15 minutes per day and gradually work your way up. A combination of resistance training and cardiovascular training is best.
  4. Stop doing active mental work at least one hour before bed. 
  5. Avoid watching TV, using a phone, laptop, or tablet before bed. The blue light from screens has been shown to worsen sleep. The bed should be used for sleep and sex only. 
  6. Create a bedtime ritual to follow every night before bed, warm bath, mindfulness exercise, gratitude journal, reading, or listening to music. 
  7. Do not use alcohol as a way to promote sleep. Alcohol negatively impacts sleep architecture and the sleep you do get will be unsatisfying. 
  8. The bedroom should be dark, quiet, and the temperature should be cool but not cold around 65 degrees is ideal. Consider blackout curtains, a fan to cool the room, and ear plugs to facilitate these conditions. 
  9. Restrict Food and drink 2-3 hours prior to bedtime. This will reduce the chances of sleep being interrupted to use the bathroom.
  10. If you have any pain, take appropriate pain medications prior to bed. 

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 

Lifestyle Psychiatry and the Gut Microbiome

  • 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. 

Lifestyle Medicine for Psychiatry: Lessons in Being Resilient

In this video I focus the discussion on the exercise/physical activity portion of lifestyle medicine for psychiatry. Exercise is an underrated and underutilized tool for fighting depression. It can have a profound impact on mood, and helps people learn to be more resilient.

Key Findings Include: 

  • For resistance training, higher intensity and shorter duration provides improvement in mood symptoms 
  • For aerobic exercise, durations of 45-60 minutes appear to provide the most improvement in mood symptoms. Longer and shorter durations showed less benefit. 
  • Keep it simple and just get started. There are a million different programs, and you can easily find yourself worrying to much about getting all the information and not enough time worrying about exercising.
  • The simplest way to start is with a daily walking routine. Spend six months consistently walking for 45-60 minutes. That’s it, no special equipment or significant out of pocket expenses required. 
  • A walking routine will set the foundation for adding additional forms of exercise including resistance training

Naltrexone For Opioid Use Disorder and Alcohol Use Disorder

MOA: mu opioid receptor antagonist which prevents exogenous opioids from binding blocking the pleasurable effects of opioid use. Reduces alcohol consumption through modulation of the opioid system, blocking the reinforcing effects of alcohol. 

FDA Indications: alcohol use disorder (oral or injectable), Prevention of relapse to opioid dependence (injection)

Oral Dose: 50 mg/day 

Injection Dose: 380 mg/month 

Caution: patient must be opioid free for 7-10 days prior to starting, conformed with a negative urine 

For alcohol use disorder start with 50 mg/day or 380 mg/month for IM formulation (injection may be preferred because it eliminates the daily decision to take the medication) 

Side effects: nausea, vomiting, decreased appetite, dizziness, injection site reaction, life-threatening side effect is hepatocellular injury in overdose 

Who is it good for?: Those ready to abstain completely from alcohol and for binge drinkers. Good evidence for reducing heavy drinking days. There is some risk of apathy or loss of pleasure with chronic use. The combination of naltrexone and bupropion has been used as a treatment for obesity. 

Pramipexole for Treatment Resistant Depression

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

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