We all know that medication use for psychiatric disorders in kids has been increasing over the past 10 years, and that it plays an important role in treatment. We also know that side effects can cause alarm among parents and young patients.
In the name of providing the best treatment (ie, making sure patients take their medication), psychiatrists may be reluctant to emphasize and assess for medication adverse effects. This creates a mismatch between the patient’s and the prescriber’s attention to side effects, which may ultimately result in lower adherence. Not to mention that briefing parents and, in developmentally appropriate ways, children and adolescents on side effects of medications is essential to ethical informed consent before starting any treatment, and asking about side effects at every appointment is similarly essential to good medical practice.
By increasing your awareness of common side effects, and how to effectively anticipate and manage them, you will help your patients achieve better outcomes by improving adherence and monitoring efficacy and response.
Much of the data on using these medications in children are extrapolated from studies in adults. However, as with most things, children are not “little adults.” They metabolize and react to medications differently from adults.
Due to differences in body size, proportions of body fat and body water, and blood protein levels, kids have a smaller volume of distribution and faster metabolism and elimination (Vitiello B. Developmental aspects of pediatric pharmacology. In: McVoy M & Findling RL, eds. Clinical Manual of Child and Adolescent Psychopharmacology, 2nd Ed. Arlington, VA: American Psychiatric Publishing; 2013:1-30). This may mean that medications that you regularly dose once daily in adults need to be dosed twice daily in your pediatric patients, and that children are more susceptible to withdrawal effects.
In general, the best approach to managing side effects is by non-pharmacological means. Often, side effects can be relieved by reducing the dose or titrating the dose more slowly. (“Start low and go slow” is a useful maxim.) The next step is to stop and switch to a different medication in the same class. If these approaches are not an option or are not clinically indicated, you can think about adding medication to manage side effects.
Another helpful principle is to assess for baseline symptoms that may later be incorrectly attributed to medication. For example, apathy can be a symptom of pediatric depression, and it is also a potential side effect of longer term use of antidepressants.
Having a collaborative relationship in which side effects are discussed on an ongoing basis will help you gauge progress, without falsely attributing a symptom to a medication or misinterpreting a side effect as part of the disorder you are treating.
These are by far the most commonly prescribed psychiatric medications in kids, as a class prescribed to 3.9% of adolescents (Olfson M et al, JAACAP 2013;52(4):378-388). Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed in this class, followed by serotonin-norepinephrine reuptake inhibitors (SNRIs), and much less commonly, tricyclic antidepressants.
Although generally well tolerated, SSRIs and SNRIs have some common, mostly idiopathic side effects, such as headaches, stomach upset, and fatigue. These are not dangerous and often go away after a period of one to two weeks, but may return with dose increases. encourage patients to stick with it for this short period of time to see if they will adjust to the medication. You can also consider changing the timing of medications to lessen the impact of side effects on functioning (eg, if your patient is feeling fatigued, switch to nighttime dosing).
The most serious adverse effect to monitor for with SSRIs and SNRIs is increased suicidality. There is some evidence of a modest increase in reported suicidality in people less than 24 years old, although there does not appear to be an increase in completed suicides (Hammad TA et al, Arch Gen Psychiatry 2006;63:332-339). This usually occurs in the first month of treatment, and as with any intervention, you must weigh the risk against the potentially life-saving benefit of treating the underlying mood or anxiety disorder. In fact, in 2004 and 2005, after the initial warnings about suicidality in young people treated with SSRIs, there was a decrease in the prescription rate of SSRIs and an increase in death from suicide in children and adolescents in the United States and the Netherlands (Gibbons et al, Am J Psychiatry 2007;164(9):1356- 1363).
If your patient does experience new or worsening suicidal thoughts, you should stop the medication and determine if a higher level of care is needed. Alternative medications, such as other SSRIs or atypical antidepressants like buproprion (Wellbutrin), should be considered, and the patient should be closely monitored.
Especially in patients with a family history of bipolar disorder, pediatric patients should be monitored for treatment emergent mania, which appears to occur in less than 2% of patients (Goldsmith M et al, Paediatr Drugs 2011;13(4),225-243). More common (2% to 10%) is general activation, such as restlessness or akathisia, silliness or giddiness, and perhaps difficulty sleeping. Propranolol can help with akathisia, as can lowering the dose or switching to a different SSRI. [For a critical analysis of SSRIs, see “A commentary on Editor’s Perspective: Do Antidepressants Work in Kids?” CCPR, October 2010.]
Stimulant medications are used primarily to treat ADHD. Side effects relevant to children and adolescents fall into three categories: cardiovascular, growth, and psychiatric (Posner J & Greenhill L. Attention-deficit/hyperactivity disorder. In: McVoy M & Findling RL, eds. Clinical Manual of Child and Adolescent Psychopharmacology, 2nd Ed. Arlington, VA: American Psychiatric Publishing; 2013:31-95).
Elevations in heart rate and blood pressure can occur, and should be monitored, but appear to be clinically insignificant for most kids. Growth slowdown is infrequent, inconsistently demonstrated in studies, and likely has very little clinical significance. Nonetheless, parents and kids may report low appetite (Posner & Greenhill ibid). Height and weight should be monitored on a regular basis.
If feasible, medications can be withheld when ADHD symptoms are unlikely to interfere with the child’s activity (eg, on weekends, vacations from school). Parents can plan to give the child a large breakfast before the stimulant medication, and can supplement intake with milkshakes and meal replacement shakes. Another option is to switch to a shorter acting medication, a different stimulant medication, or to non-stimulant treatment—for example with atomoxetine (Strattera) or clonidine (Kapvay)—or to add an appetite stimulant like cyproheptadine (Periactin). Finally, the emergence of true psychosis is uncommon but is reason for immediate cessation of the medication.
There are two categories of side effects to consider with these medications: neuromuscular and metabolic. First generation antipsychotics are thought to have worse neuromuscular adverse effects, while second generation antipsychotics (SGA) are notorious for causing metabolic derangements. However, either class can cause both groups of side effects. Pringsheim T et al (Paediatr Child Health 2011;l6(9):590-598) offer a summary of neurological side effects such as akathisia, withdrawal akathisia, tardive dystonia, and tardive dyskinesia and their management for antipsychotic use in children. Here, we will focus on SGAs and their characteristic metabolic side effects, given the increasingly common use of this class in pediatric mood, behavior, and psychotic disorders.
Metabolic effects of SGAs include weight gain, dyslipidemia, and increased blood sugar. One observational study showed weight gain of up to 20 pounds within two and a half months of children starting olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), or aripiprazole (Abilify) (Correll CU et al, JAMA 2009;302(16):1765-1773). The risk appears greatest with Zyprexa, clozapine (Clozaril), and Seroquel, and less, but still present, with Risperdal and Abilify (PringsheimT et al, Drug Saf 2011;34(8):651-668).
Addressing issues of weight with children and adolescents should be done with a nonjudgmental, collaborative approach. Cognitive behavioral therapy and nutrition counseling are evidence-based interventions in adults treated with SGAs to minimize weight gain or, in some cases, result in modest weight loss. Although there are not studies evaluating these interventions in kids, they should nonetheless be considered (Maayan L & Correll CU, Expert Rev Neurother 2010;10(7):1175-1200).
There are some expert, largely common sense guidelines that outline non-medication approaches, such as encouraging physical activity that kids find enjoyable, limiting screen time, and enlisting family involvement with planning healthy meals (Maayan & Correll op cit). If the metabolic abnormalities persist, the dose of the SGA should be lowered if clinically feasible. Switching to an alternate agent that is associated with less weight gain is a reasonable approach. For elevated glucose, you should consider consultation with an endocrinologist, as the addition of some medications such as metformin may help ameliorate the effects (Ho J et al, Paediatr Child Health 2011;16(9):575-580).
Lithium and divalproex sodium (Depakote) are the two most commonly used mood stabilizers for pediatric bipolar disorder. The most common side effects of lithium, FDA-approved for use in children 12 years of age and older, include gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) and nervous system problems (headache, dizziness, tremor, and somnolence). GI symptoms may improve if you switch to prescribing coated capsules of lithium, called Lithobid, or if doses are split into two or three times daily.
Tremor is reversible only with a decrease in dose or cessation of the medication. One in five patients will report increased thirst and changes in appetite (Findling RL et al, J Child Adolesc Psychopharm 2011;21(3):195- 205), and acne is commonly reported as well. Acne is particularly pertinent to young patients’ adherence, and referral for dermatologic treatment may help. Due to a narrow therapeutic window, regular levels need to be checked and kidney and thyroid gland function must be monitored (Thomas T, Kuich KW, & Findling RL. Bipolar disorders. In: McVoy M & Findling RL, eds. Clinical Manual of Child and Adolescent Psychopharmacology, 2nd Ed. Arlington, VA: American Psychiatric Publishing; 2013:227-267).
Divalproex sodium is an anti-seizure medication used in the treatment of bipolar disorder (Thomas T et al, Pediatr Clin N Am 2011;58:173-187). GI side effects include nausea, vomiting, and diarrhea, and can be lessened by taking the medication with food or switching to Depakote, the coated version of this medicine. You can relieve effects on the central nervous system, such as headache, sedation, and cognitive slowing, by splitting doses, giving the medication at bedtime, or reducing the dose (Thomas, Kuich, & Findling op
Since divalproex sodium can cause life threatening liver and pancreas problems, any serious abdominal pain or ongoing vomiting or diarrhea should be evaluated urgently by checking a blood level and checking liver function tests, and may warrant stopping the medication. Female adolescent patients should also be educated on fetal risks if they become pregnant, as well as symptoms of polycystic ovarian syndrome (PCOS), such as hirsutism and irregular periods.
CCPR’s VERDICT: Prescribing psychiatric medications to your pediatric patients can have enormous benefits, but necessarily comes with the risk of side effects. For clinicians treating this vulnerable population, adverse effects must be treated with particular vigilance and awareness. By enhancing your understanding of psychotropic side effects, you will be better equipped to provide anticipatory guidance, manage concerns and symptoms as they arise in the course of treatment, and ensure the best possible outcome.