Gabapentin/Neurontin The Most Common off-Label Prescription in Psychiatry 

Introduction 

Gabapentin is approved by the FDA for three specific indications to prevent and control partial seizures, relieve nerve pain following shingles (post herpetic neuralgia), and to treat moderate to severe restless leg syndrome. Unfortunately, less than 1% of the prescriptions written for gabapentin are for the above listed FDA approvals. In fact, much of the off-label prescribing of gabapentin is done for the treatment of psychiatric and substance use disorders. 

We were first alerted to the misleading marketing practices when Pfizer paid a $2.3 billion dollar fine for misleading clinicians through their marketing campaigns. Gabapentin is often thought of as a benign medication that can address symptoms in several common disorders including migraine, chronic pain, fibromyalgia, opioid use disorder, anxiety, and mood disorders. There is now mounting evidence that this medication is not as safe as people once assumed yet many of these prescribing practices continue despite a lack of quality data. Today we will review the safety and efficacy of gabapentin in psychiatric disorders. 

How Does Gabapentin Work?

Gabapentin functions by binding to the alpha-2-delta subunit of voltage gated calcium channels theoretically offering antipain, anticonvulsant, and anxiolytic properties. Although it’s structurally related to the GABA neurotransmitter, there is no direct interaction at GABA A or B receptors. 

Why is there such an increase in Gabapentin prescribing?

In the United States the opioid epidemic drove much of the 64% increase in gabapentin prescriptions 2012 to 2016 as policy makers searched for safer alternatives for pain management. Although lacking any data for the treatment of chronic pain, gabapentin was elevated into this role because of several factors cost, non-controlled status at the federal level, evidence in neuropathic pain, and benign side effect profile. 

However, the risk for gabapentin abuse became apparent as more prescriptions were written. The risk of adverse effects was prevalent when combined with other CNS depressants such as opioids, the exact thing gabapentin set out replace. Approximately 15%-22% of people with an existing substance use disorder abuse gabapentin. Those who overused gabapentin were found to be at increased risk of all-cause or drug-related hospital stay and emergency visits for altered mental status and respiratory depression. 

The off-label prescribing of gabapentin comes with risk. 

Evidence For Use in Anxiety Disorders

The evidence for gabapentin’s use in anxiety disorders comes from only two industry sponsored studies with a total of 172 participants. These are relatively small but well-designed studies that provide limited evidence for the use of gabapentin in anxiety disorders. The first study was in 1999 and looked at the use of gabapentin in social anxiety disorder. 69 participants were randomized to placebo or gabapentin 900-3600 mg/day for 14 weeks. A significant reduction in social anxiety was observed over the 14 weeks and the conclusion was more studies were needed to confirm the results. The other study looked at panic disorder with the same study design and doses of gabapentin, only this time the study lasted 8 weeks. The results indicated gabapentin was effective for severe panic disorder. One thing we notice is neither of these studies focused on generalized anxiety disorder. These results have not been replicated in other studies. 

There is far more evidence for the use of pregabalin in anxiety disorders. In Europe it does have regulatory approval for generalized anxiety disorder. 

Evidence For Use in Bipolar Disorder 

I’m going to burst this bubble and maybe a few other bubbles up front. While some believe all anticonvulsants are “mood stabilizers” they are wrong. Gabapentin has never proven in RCTs to treat mania or any other aspect of bipolar disorder. Likewise, Topiramate and oxcarbazepine have performed poorly in studies assessing their efficacy in bipolar disorder. Simply put, if you are on any of the three medications as primary mood stabilizers it’s best to consider other options such as lithium. 

Evidence For Use In Alcohol and Cannabis Use Disorder  

While addiction treatment is part of the reason we are in this mess with gabapentin, it does have a role in alcohol use disorder (AUD) and cannabis use disorder. The APA added gabapentin as a second line option for AUD because patients who take it for this indication report fewer heavy drinking days with an effect size in the moderate range. There is also some indication that sleep quality improves with gabapentin when patients are cutting back or stopping alcohol use. Alcohol is known to worsen sleep with more frequent nighttime awakenings. The dose range is 300-3600 mg/day in divided doses with many using an average of 900 mg/day. 

Gabapentin is sometimes used for alcohol withdrawal in place of benzodiazepines or phenobarbital. There were a few seizures in the gabapentin groups raising some questions about its use in severe alcohol withdrawal. It’s probably best left for those with less severe dependence. 

Typical Taper for Alcohol Withdrawal

-Start with 1200-2400 mg/day in three divided doses 

-Taper to 600 mg/day over the course or 4-7 days watching for objective signs of alcohol withdrawal and have Ativan available should a seizure develop. 

-Taper by 300 mg/day over the next 2-3 days until the medication is completely off. 

In cannabis use disorder there is limitted data. A single study showed improvement in withdrawal symptoms, reduced cannabis use, and improved executive function but this is not enough to recommend gabapentin on a regular basis in clinical practice. 

It’s important to note gabapentin failed in controlled trials for cocaine, methamphetamine, benzodiazepine, and opioid use disorder. It’s dangerous to combine gabapentin and opioids as discussed earlier in the video. 

A Quick Note on Gabapentin for Chronic back pain 

There are 8 total studies including a systematic review and meta-analysis to assess pain relief in patients with chronic lower back pain a reason many patients tell me they are taking gabapentin for. When you pool this data together, gabapentin demonstrated minimal improvement in pain compared to placebo and had an increase in adverse effects including dizziness, fatigue, and visual disturbances.

Adverse Effects 

The most common side effects include sedation, fatigue, dizziness, imbalance, tremor, and visual changes. 

Dosing

Gabapentin has a short half-life of 6 hours and will need to be dosed three times per day. The kinetics of gabapentin are not linear which means levels in the blood do not rise consistently. For a 900 mg dose, only 540 mg is absorbed. This has to do with the transporters responsible for gabapentin absorption becoming over saturated limiting the amount of medication absorbed. 

Conclusion

While there are very good reasons to consider the use of gabapentin many of the common reasons cited in clinical practice lack the appropriate evidence to support using the medication. It’s best to stick with FDA approved indications and if you are prescribing it off-label consider only using it for the disorders with the most evidence in my opinion that is alcohol use disorder when other treatments have failed. 

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 Most Feared Side Effect of antipsychotic Medication

Introduction: 

I get a lot of questions about the risks and side effects associated with antipsychotic medications. These medications are no longer used exclusively in schizophrenia, and they are now widely accepted as treatment for bipolar disorder, adjunctive therapy for depression, and even severe anxiety disorders resistant to other medications. 

As a result, more people than ever are being prescribed these medications and many are concerned about the risk of side effects. One that I get asked about all the time and maybe the most feared of all side effects is the often-irreversible movement disorder called tardive dyskinesia (TD). 

This discussion and video will help you understand the risk of developing TD and the approaches to managing it should symptoms develop. 

EPS and Dopamine Blockade: 

Dopamine receptor blockade can cause a variety of movement disorders, after all dopamine is directly involved in the process of movement. We call the movement disorders associated with dopamine blocking medication extrapyramidal syndromes (EPS). 

Most EPS develop shortly after staring medication and are treatable with medication and stopping the offending agent. This is not the case for TD. There is a delay in the onset of symptoms (tardy) and persistence of the symptoms well after the medication has been stopped. 

TD can develop after medication is used for a few months, or as little as a few weeks in the case of elderly patients. TD can also occur when a medication is discontinued or reduced. 

Myths About TD: 

  • The longer you stay on an antipsychotic the more likely you are to develop TD. The prevalence (proportion of people who have a condition at or during a particular time) of TD increases with time, but the incidence (number of new cases) decreases with time. 
  • With first generation dopamine blockers 40-50% of patients developed TD but not in a linear fashion. Half of the patients developed TD within the first 5 years of taking medication. The incidence is about 5% per year over the first 5 years and then the incidence decreases to 1-2% per year and levels off after that. 
  • TD is more likely to occur in the first few years of treatment and less likely after 5 years of treatment. 
  • The risk of TD does not increase if acute EPS occurs and does not decrease if no acute acute EPS develops

Risk factors for the development of TD: 

  • Diagnosis of schizophrenia 
  • Older age 
  • Female sex 

Schizophrenia itself causes TD and has been described in the literature long before medications were used as treatment. The prevalence was lower about 5-10% Vs 40% seen after medications were used in treatment. This occurs because schizophrenia is not just a disease of the cortex it also involves the basal ganglia which is responsible for the movement disorders. 

TD Risk at 1 Year of Treatment: 

  • Risperidone 0.6% 
  • Olanzapine 0.5% 
  • Haloperidol 2.7% to 4.5% 

It’s clear from this data that first-generation dopamine blocking medications have a much higher rate of TD compared to the second-generation medications. This 0.5% rate is similar to the rate seen in the natural course of illness in schizophrenia (essentially the same as placebo). 

In patients with mood illnesses who use dopamine blocking medications there are very low rates of TD. It can occur in mood disorders but it’s very infrequent and does not occur at nearly the same rates seen in schizophrenia.

The risk of TD is associated with the underlying pathology of schizophrenia which is distinct from other mood disorders. 

Treatment of TD:

For a long time, there was no treatment for TD. In the last few years two medications have been developed Valbenazine (ingrezza) and deutetrabenazine (Austedo) both of which are FDA approved. 

The mechanism of action of these two medications is VMAT-2 inhibition. Vesicular monoamine transporter 2 inhibition results in decreased monoamine activity at the synapse. 

The studies used to gain FDA approval of these medications showed a mild improvement on the abnormal involuntary movement scale of 2-3 points in patients with mild TD. 

It’s important to keep in mind TD did not go away fully but it did improve over placebo. 

The best treatment for TD is to stop the dopamine blocker. In some cases, if the dopamine blocker is stopped early enough TD is reversible. In many cases the medications are continued because there are no other clinical options and you are left with treating TD with VMAT-2 inhibitors. 

The Best Antipsychotic Medication in The World 

Introduction:

I’ve said it before in previous videos, older medications are more effective and newer medications have fewer side effects. 

The advent of SSRIs in the late 1980’s and early 1990’s was largely driven by safety and not efficacy. The same is true for antipsychotic medications. This may be the reason most people haven’t even heard about Clozapine (brand name Clozaril). 

Efficacy

Clozapine is the single most effective antipsychotic available, and it works in treatment resistant schizophrenia where no other medication is proven to be effective. 

The results speak for themselves, 30% of previously treatment resistant patients experience symptom reduction within 6 weeks and that number jumps to 60% after 6 months of treatment. 

Clozapine has a slew of additional benefits including mood stabilizing prosperities (it can be used in bipolar disorder), reduction in psychogenic polydipsia and the hyponatremia associated with it, reduction in hostility and aggression, reduction in the risk of suicidal ideation, improvement in substance use, and it may even help patients quit smoking a difficult task in schizophrenia. 

So why are most schizophrenic patients not on this medication if it’s so great? 

Side effects, side effect, side effects

-Sedation: feeling tired this can largely be mitigated by dosing the medication at night before bedtime. 

-Tachycardia: It’s worth getting an EKG in patients with preexisting heart conditions or those at high risk due to hypertension and hyperlipidemia 

-Sialorrhea: excessive saliva production leading to drooling, no one wants this 

-Dizziness

-Constipation: this should be addressed immediately if a patient complains about it as it can lead to serious complications. In many cases Senna and Colace will do the trick

-Orthostatic hypotension 

-Weight gain 

Serious and potentially fatal Side effects include: 

-Agranulocytosis: decreased absolute neutrophil count which can result in increased risk for serious infection and the reason everyone on the medication gets weekly blood draws for the first 6 months 

-Seizures: clozapine is known to lower the seizure threshold 

-Myocarditis: inflammation of the heart usually due to a viral infection 

The risk for agranulocytosis is highest when starting treatment, usually during the first year of treatment (0.8%) and the maximum risk is between 4 and 18 weeks (when 77% of cases occur), although it can still occur at any point in the treatment.

Agranulocytosis

Monitoring is thus very important, and each patient must be registered in the Risk Evaluation and Mitigation strategy (REMS) data base before starting the medication. 

A CBC with differential must be drawn to calculate the absolute neutrophil count prior to starting treatment and then weekly for the first 6 months. Then monitoring continues every 2 weeks for the next 6 months and finally monthly after the first year of treatment. 

If agranulocytosis occurs stopping clozapine allows majority of cases to recover within 14 days. 

Now that we know that this medication is very effective but comes with a high side effect burden a natural next question might be why does the medication work? 

Mechanism of Action

Clozapine has very low affinity for the D2 receptors which is unique as most other antipsychotics will bind strongly to D2 receptors. Clozapine had far greater D1 and D4 binding affinity, blocking both receptors. 

Clozapine also has significant activity at other neurotransmitter sites. It blocks alpha receptors which may be the reason for orthostatic hypotension. It blocks histamine H1 receptors resulting in sedation and weight gain. It blocks 5-HT2A serotonin receptors and is highly anticholinergic resulting in constipation and urinary retention. 

It has two unique properties; it influences the glutamate system by altering NMDA receptor sensitivity and increases the release of brain derived neurotrophic factor BDNF. 

Metabolism And Drug Interactions

Clozapine is primarily metabolized by CYP450 1A2 and 3A4 and cigarette smoking will cause a reduction in clozapine levels due to induction of CYP 1A2. 

Before Starting the Medication

Before starting clozapine, the ANC must be above 1,500. If neutropenia develops treatment will depend on the severity of the drop. 

Mild Neutropenia: ANC 1,000-1,499, you would continue treatment and check an ANC three times weekly until it reaches 1,500. 

Moderate Neutropenia: ANC between 500 and 999, stop treatment and check the ANC daily until it reaches 1,000 then 3 times weekly until it reaches 1,500 then weekly for 4 weeks before returning to the patients prior monitoring schedule. 

Severe Neutropenia: ANC less than 500, stop treatment and check an ANC daily until it’s 1,000 then 3 times weekly until it’s 1,500. The patient should not be rechallenged without a hematology consult and clear benefits that outweigh the risks. 

Dosing

Clozapine can be started at 12.5 to 25 mg at bedtime. The dose can be increased 25 mg/day inpatient and 25 mg per week in the outpatient setting as tolerated. 

You can overlap prior treatment with another antipsychotic and tapper the old medication once clozapine dose reaches 100 mg or more. 

Plasma Levels

Clozapine dose should be based on serum levels, with a target blood level of 200 to 300 ng/ml. If there are still symptoms present the target serum level is 450 ng/ml. There are no benefits to serum levels above 900 ng/ml. 

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.

Guide To Viewing My Content

If you are new to the blog and my social media content, we should start with a brief introduction. 

My name is Dr. Garrett Rossi, I’m a medical doctor who specializes in adult psychiatry. I’m board certified by the American Board of Psychiatry and Neurology. I’ve practiced in multiple settings including inpatient, outpatient, partial care, assertive community treatment teams, and I provide ECT services.

I make mental health content on multiple social media platforms and each one has a specific style and type of content. 

Shrinks In Sneakers YouTube Click Here

This is where you can find the deep dives on mental health topics including medication reviews, psychiatric diagnosis, and various other topics. Videos can range anywhere from 5-20 minutes and time stamps are available in the descriptions for longer content. 

Shrinks In Sneakers Instagram Click Here:

This is where you can find shorter videos and posts on mental health topics. The focus on Instagram is more on mental health advocacy, and myths about psychiatry and mental illness. The content here is shorter but still has a lot of educational value. 

Shrinks In Sneakers LinkedIn:

This is where you can find more information about my professional activities. I have information about my advocacy work, professional memberships, publications, and is another good place to follow my work. I make frequent posts here as well. 

Shrinks In Sneakers Twitter

Here I’m not very active and haven’t spent much time but I do update blog posts and other relevant information here as well. 

If you have a question or want to get in touch with me, I am most active on YouTube, LinkedIn, and Instagram. 

We are building a community where empathy is a central part of the content. The goal is to make psychiatry more accessible, provide education, and reduce stigma associated with mental health treatment. 

New Treatment for Acute Agitation

The FDA has approved dexmedetomidine sublingual film for the treatment of agitation associated with schizophrenia or Bipolar I/II disorder in adults.  

When agitation and aggression are severe, swift resolution of the situation is required.

Introduction:

Since the advent of chlorpromazine in the 1950’s pharmacological intervention has been a mainstay in these acute situations. In many cases the combination of haloperidol, lorazepam, and diphenhydramine, the so called B-52 are administered intramuscularly when quick resolution of agitation is required for the safety of the person and staff. 

But what happens when these methods fail to provide adequate relief and person remains agitated?

There are few options available outside of the dopamine blocking medications and benzodiazepines. 

I’ve been in situations as an early career psychiatrist where I’ve had to treat severe agitation that is unresponsive to the traditional methods of treating agitation. 

After multiple medications failed to adequately treat the agitation, I called the medical floor to transfer the person for a Dexmedetomidine (precedex) drip. This is a medication I’ve seen work well in the ICU setting with agitated delirium. 

But drips are complicated to use and require careful monitoring on the medical floor. I was thinking it would be great if there was an option that did not require IV placement or transfer to the medical floor. 

Mechanism of Action:

Recent studies have looked at sublingual Dexmedetomidine as a potential new treatment for agitation. 

Dexmedetomidine is an alpha-2 noradrenergic agonist approved by the FDA for IV sedation and analgesia and limitted to 24 hours. It induces sleep by activating alpha-2 presynaptic receptors reducing norepinephrine release. Both sedation and awakening are rapid, and the medication is safe but does require monitoring of blood pressure and heart rate. 

Phase 3 Clinical Trial Results:

A phase 3 clinical trial of 120 micrograms and 180 micrograms of sublingual dexmedetomidine was compared to placebo in patients with bipolar disorder. They used the excited portion (PEC) of the PANSS to measure efficacy and found a response beginning at 20 minutes and continuing to 120 minutes at both doses. 90% of participants in the 180 microgram and 76% in the 120 microgram groups achieved a response. No significant adverse events occurred in the treatment groups.  

Hsiao JK. Sublingual Dexmedetomidine as a Potential New Treatment for Agitation. JAMA. 2022;327(8):723–725. doi:10.1001/jama.2021.21313

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. 

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