General Prescribing Principles of Psychotropic Medication

General Prescribing Principles of Psychotropic Medication

When starting psychiatric medication, it is important to understand the intended symptomatic relief provided by the medication and discuss this with the family. This allows the patient and the family to have realistic expectations of what medications can and cannot do.

Treatment response should be monitored regularly. Tools that are used to screen for mental health conditions may be helpful to track response to interventions. If medications do not produce symptom relief, healthcare professionals are advised to consider the following next steps.

  • Assess whether the dose and timeframe are adequate to have an impact on symptoms.
  • Assess whether the child is taking medication as prescribed.
  • Consider alternative medications.
  • Optimize psychosocial treatment.
  • Reevaluate diagnosis.
  • Consider comorbid conditions and substance use.
  • Determine whether pharmacogenetic testing may be appropriate.

Meet Angela

Angela is a 9-year-old girl being seen by her primary care provider for inattention and poor academic performance. Vanderbilt Assessments from parents and teacher are suggestive of ADHD, inattentive type. She is prescribed an extended-release methylphenidate extended release at a dose of 18mg daily. After two weeks, the family and teacher report no side effects but no improvement.

The primary care provider believes that the time frame, two weeks, is adequate to see what the response to that dose is. She increases the dose to 27mg for two weeks, which is well tolerated and shows mild improvement. Over the next two months, the dose gradually increased to 54mg daily. At this dose, the family and teacher note that she is more attentive in class and less forgetful. However, her appetite has sharply reduced, and she has had some unintentional weight loss, and her academic achievement such as reading has not improved.

The primary care provider reduces the dose of methylphenidate to 45 mg (a 27tab plus an 18mg tab) which improves appetite and suggests that the family request educational assessment through the school district, a process which takes several months. The results of the testing suggest the presence of a reading disorder (i.e., dyslexia), and special education services are initiated. By the end of the school year, her inattentive symptoms are significantly improved, and an IEP is in place with considerable progress made in Angela’s reading goals, and her grades are improved.

Insurance Coverage

For information about insurance coverage for youth enrolled in Medicaid, see the Ohio Department of Medicaid preferred drug list.

 

Pharmacogenetic Testing

While many hope that pharmacogenetic testing will allow them to understand which medications “work best” for patients, this is not entirely accurate. Pharmacogenetic testing analyzes the genetic-based variations of liver enzymes present in a patient. Some variations allow for quick breakdown of medications and others for slower breakdown. Pharmacogenetic testing may be used to understand individual differences in the metabolism of medications and the propensity for side effects based on which liver enzyme breaks them down, but it does not establish which medications work best for a person’s individual symptoms. The mechanisms of action of psychotropic medications occur at the neuronal receptors and there is no current testing for variation in these receptors. Pharmacogenetic testing is not routinely recommended. Treatment decisions should be based on evidence-based prescribing guidelines, regardless of the results of pharmacogenetic testing.

 

Shared Decision Making

 

Shared decision-making encourages children, teens, and caregivers to have a voice in their care. The Ohio Minds Matter Shared Decision-Making Toolkit is a guide for youth and families to take an active role in their treatment, prepare for their appointment, consider treatment options, document their symptoms, and describe their goals.

 

Stimulant Prescribing Principles

Although the weight and size of patients can give clues about what doses of stimulant medications will be appropriate to treat ADHD symptoms, there is enough variation in effective doses that a general principle of starting with dosages at or near the bottom end of the dose range, is a good practice. Fortunately, both the beneficial and adverse effects of stimulant medications are usually seen within a few days of starting the medication allowing for rapid determination of stimulant dose effectiveness and tolerability. This means that with a few reliable data points combining patient self-report, observation from caregivers, and information from collateral sources (such as teachers), decisions about increasing, decreasing, or maintaining a medication dosage can be made. Often, increments of 1-2 weeks are a good interval to allow for observations to be collected. Although some caregivers think it may be best not to share medication changes with school staff, thinking this may bias their observations, in many cases informing school staff and proactively soliciting their observations yields better information for refining the treatment plan.

Common adverse effects of stimulant medication are lowered appetite, sleep disruption, feeling nervous or jittery, adverse changes in mood or behavior (either when the medicine is active or when it wears off), headaches, stomachaches, and mild increases in heart rate or blood pressure. Adverse effects are usually, but not always, dose-related, with dose reduction often leading to resolution. Because stimulant medications have a specific duration of activity, one of the most helpful pieces of information to gather about adverse effects is their timing and severity throughout the day (e.g., about an hour after taking a stimulant dose, suggesting a direct adverse effect of the medication, or about 8 hours after taking a long-acting stimulant, suggesting an adverse effect related to when the medicine wears off). This will help guide medication adjustments to address adverse effects. For prescribing guidance, view the Stimulant Medication Aid.

 

Nonstimulant ADHD Medication Prescribing Principles

Nonstimulant ADHD medications, as a group, improve ADHD symptoms in fewer patients and to a smaller degree than stimulant medications. However, they may be a good choice for some patients, either alone or in combination with stimulant medications. The prototypical patient for whom nonstimulant ADHD medications are helpful is one who has not been able to tolerate adverse effects of stimulant medication. Another group is patients whose caregivers are especially averse to stimulant medication. Sometimes those caregivers can be reassured that stimulant medications are some of the best- and longest-studied medications for youth, and that we have a large amount of clinical experience to demonstrate that they are generally safe and effective.

FDA-approved nonstimulant ADHD medications can be divided into two basic groups: alpha agonist medications (guanfacine and clonidine) and norepinephrine reuptake inhibitors (atomoxetine and viloxazine). Among the alpha agonists, guanfacine has more specificity for the brain targets of ADHD therapy, so it generally has fewer adverse effects compared with clonidine. However, both can cause sedation, lightheadedness (especially when standing up), orthostatic hypotension, and headache. For norepinephrine reuptake inhibitors, common adverse effects are gastrointestinal side effects, reduced appetite (although usually milder than seen with stimulant medications), and mild changes in mood and irritability.

For prescribing guidance, view the Nonstimulant Medication Aid.

 

SSRI Prescribing Principles

When starting an SSRI medication in a patient who has never taken this type of medication, it is important to start at a low dose for the patient’s age and weight. This allows clinicians to assess the patient’s tolerability of the medication. After two weeks, the medication should be increased in regular intervals (2 to 4 weeks) until the patient’s symptoms are significantly improved or they cannot tolerate a dose high enough to achieve symptom relief or the maximum dose of the medication is reached.

SSRIs carry a Box Warning due to a rare but significant risk of increased suicidality in the initial stages of treatment. It is important to talk about the boxed warning with families during medication management visits and direct them to notify a provider if suicidal thoughts or behaviors develop or intensify. Most studies suggest that the potential benefits of adding SSRI treatment for moderate to severe anxiety or depression treatment far outweigh the minimal potential risk that patients will experience increased suicidal ideation.

For prescribing guidance, view the SSRI Medication Aid.

 

Typical Starting Doses of SSRI’s:
Medication Pre-pubertal Children Peri-pubertal Children Post-pubertal Adolescents
Fluoxetine 2.5- 5 mg 5-10 mg 10 mg
Escitalopram 1- 2.5 mg 2.5 mg 5-10 mg
Sertraline 12.5 mg 12-25 mg 25- 50 mg

 

“Failure” of an SSRI Medication

To say that a patient has failed a trial of an SSRI, they must have reached a maximum tolerated dose for four weeks and have been on medication for a total time of over eight weeks without receiving meaningful benefit.

  • Example: 12 y/o patient started on fluoxetine 5 mg and titrated up to 20 mg without side effects or symptomatic relief over 12 weeks. This is not a treatment failure as they did not reach a maximum dose, either by tolerability or dosing threshold. This patient should have the fluoxetine increased.
  • Example: 16 y/o patient started on escitalopram 10 mg and increased to 20 mg over eight weeks. Patients had significant somnolence and GI symptoms at the higher dose and did not achieve symptom relief. Escitalopram should be discontinued due to treatment failure.

 

Cross Tapering

When a patient has failed their first SSRI, the next step is to switch to another SSRI. This can be done by cross tapering or starting a second medication and increasing its dose at the same time the first medication is being weaned down. One can think of this as going up on the dose of a new medication in a stepwise manner while going down on the dose of the ineffective medication in the same stepwise manner. This approach reduces potential side effects that can emerge at the time of SSRI discontinuation and allows clinicians to achieve dose equivalence of the newly started SSRI relatively quickly. There are no agreed upon time intervals for dose adjustments during a cross taper. In general, dose changes can take place after a few days or a week. The longer a patient has been on a medication, the longer it should take to wean.

Example of a Cross Tapering Schedule: patient currently on fluoxetine 40 mg and switching to sertraline

  • week 1: decrease fluoxetine to 20 mg and start sertraline 25 mg
  • week 2: decrease fluoxetine to 10 mg and increase sertraline to 50 mg, check in with clinician
  • week 3: stop fluoxetine and increase sertraline to 100 mg
Approximate Dosing Equivalents
SSRI Step 1 Step 2 Step 3 Step 4
Fluoxetine 10 mg 20 mg 40 mg 60 mg
Sertraline 25-20 mg 50-100 mg 100-150 mg

200 mg

Escitalopram 5 mg 10 mg 20 mg 30 mg

 

Managing Side Effects of SSRIs

When in doubt, decrease dose and consult with a psychiatrist.

Patient Reports Clinical Description Action to Consider
Uneasy restless feeling, need to move legs/walk around, diaphoresis Akathisia Lower dose, titrate slowly
Restlessness, increased impulsivity, difficulty falling asleep Activation Lower dose, titrate slowly
Dizziness, nausea/emesis, h/a, gait instability, myalgias, fatigue Withdrawal syndrome Restart or reinstate low to moderate dose
Clonus, disorientation, increased blood pressure, fever Serotonergic toxicity Reduce drug interactions, seek consultation in severe cases
Bizarre behaviors, not sleeping for days, rapid speech, extreme irritability Mania (rare) Stop medication and consult with psychiatrist

 

SSRI Discontinuation

The goal of treatment with SSRIs is to achieve symptom remission. Once a patient has significant improvement in their symptoms, an SSRI should be continued for 12 months before it is weaned off. In this instance, the SSRI should be weaned slowly to allow for adequate monitoring of potential symptom recurrence.

Example of discontinuation schedule: 15 y/o patient has been on fluoxetine 40 mg for 12 months with symptom remission

  • Month 1: fluoxetine 30 mg daily and follow up visit to monitor symptoms
  • Month 2: fluoxetine 20 mg daily and follow up visit to monitor symptoms
  • Month 3: fluoxetine 10 mg daily and follow up visit to monitor symptoms
  • Month 4: stop fluoxetine

 

Antipsychotic Medications

These medications should be used with caution in the primary care setting. The general term “antipsychotic” relates to the fact that medications in this class are used to treat schizophrenia, although schizophrenia and other mental health conditions with psychosis are rare in youth. Older medicines in this group are sometimes called “first generation antipsychotics” or FGAs and newer medicines in this group, which are used much more frequently and have some differences in their chemical effects from older agents, are sometimes called “second generation antipsychotics” or SGAs. In the pediatric population, SGAs are most often used to treat severe mood and/or aggressive behaviors. Most of this use is off label and comes with significant risk to patients, and proper use of these medicines involves weighing the risks and benefits of these medications and monitoring for common side effects.

For prescribing guidance, view Antipsychotic Medication Aid.

 

There are some FDA-approved indications for SGAs, as outlined below:
Condition Aggression in patients with autism spectrum disorder Bipolar disorder* Schizophrenia
SGA with FDA approval Aripiprazole (ages 6 and older) Risperidone (ages 5 and older) Aripiprazole (ages ≥ 10) Asenapine (ages ≥ 10) Lurasidone (ages ≥ 10) Olanzapine (ages ≥ 13) Risperidone (ages ≥ 10) Quetiapine (ages ≥ 10 Aripiprazole (ages ≥ 13) Lurasidone (ages ≥ 13) Olanzapine (ages ≥ 13 Paliperidone (ages ≥ 12) Risperidone (ages ≥ 13) Quetiapine (ages ≥ 13)

*The specifics of FDA approvals for medications to treat bipolar disorder are complex, with differences in whether they are approved for acute manic or mixed mood episodes, maintenance of mood for patients after manic or mixed mood episodes, or depressive episodes. In situations where distinguishing between these is necessary, please consult more complete prescribing guides.

By far the most common adverse effects of SGAs are their metabolic effects. Specifically, there is a high frequency of increased appetite, weight gain, and associated health complications resulting from these medications. For this reason, it is important that youth being prescribed SGAs are routinely monitored for weight and BMI increases beyond what is expected based on growth curves, along with laboratory monitoring of fasting blood glucose, cholesterol, and triglycerides. [Please see the chart below for more detailed information on the recommended metabolic monitoring protocols.]

Another type of adverse effect related to SGA use is movement abnormalities. These are sometimes called “extrapyramidal symptoms” (EPS) and occur less frequently with SGAs than with the use of FGAs. EPS is a broad term which encompasses several distinct types of medication effects.

  • In acute dystonic reactions, there is involuntary contraction of muscles (within the face, extraocular muscles, neck, extremities, or sometimes other parts of the body) which can be uncomfortable and frightening; anticholinergic agents (diphenhydramine or benztropine) may be used to reverse acute dystonia.
  • In akathisia, patients experience an internal feeling of restlessness and a compelling urge to move. In tardive dyskinesia (TD), involuntary movements (especially affecting the face and mouth, but sometimes other parts of the body) develop after treatment with an antipsychotic medication, and this may occur months or years into treatment (“tardive”) in individuals who did not initially display these movements. In withdrawal dyskinesia, movements like those seen in TD may develop in patients who stop taking antipsychotic medication or who switch from one agent to another.
  • In neuroleptic malignant syndrome (NMS), a rare side effect of antipsychotics, severe muscle rigidity is associated with fever and tachycardia. Laboratory findings show increased creatine kinase and white blood cell counts. Patients with suspected NMS should be seen emergently because the condition, while rare overall and especially rare with SGAs, is potentially life-threatening.

Additional adverse effects of SGAs for the primary care provider to be aware of are sedation, hyperprolactinemia (especially with risperidone and paliperidone use), and QTc prolongation (especially with ziprasidone use).

Recommended monitoring for metabolic adverse effects in individuals who are taking SGAs is described below:

  Baseline 3 mo. after starting 6 monthly Annually
Complete Blood Count/differential X     X
Fasting Basic Metabolic Panel (electrolytes, BUN and creatinine, and glucose) X     X
Fasting Glucose     X  
Liver Function Tests (AST, ALT) X X   X
Fasting Lipid Panel (Total Cholesterol, LDL, HDL, Triglycerides) X   X X
Height/weight/BMI X X X X
Pulse/Blood Pressure X X   X

(Adapted from Correll CU. “Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents.” J Clin Psychiatry. 2008;69 Suppl 4:26-36.)