Psychotropic Medication Options for Common Target Symptoms

Target SymptomsMedication Class (Examples)Comments
Psychostimulants (methylphenidate, dexmethylphenidate, mixed amphetamine salts, lisdexamfetamine, dextroamphetamine)466,580587With other coexisting symptoms, medication may not appear as effective
SNRIs (atomoxetine)588590May be more sensitive to adverse effects
α-2 adrenergic agonists (clonidine, guanfacine)591594Steps:
Atypical (second generation) antipsychotics (aripiprazole, risperidone)595598• Behavioral approaches implemented
• Problems persist, trial of medication management
• Start with a low-dose stimulant (eg, methylphenidate or mixed dextroamphetamine salts) and increase as needed and tolerated
 May be most effective in children without comorbid intellectual disability
 Targets symptoms of impulsivity and hyperactivity
• If there are adverse effects or if not effective:
 Consider atomoxetine, especially if also with social anxiety
 Consider α-2 agonists (eg, short- or long-acting guanfacine, clonidine)
 Other medications (less evidence): atypical antipsychotic medications may decrease hyperactivity; their primary use is for irritability and aggression
Adverse effects:
 Psychostimulants: appetite suppression and insomnia; also irritability, depressive symptoms, and social withdrawal; it does not appear to worsen repetitive behavior or oppositional behavior
 Guanfacine, clonidine: drowsiness, fatigue and irritability; may also include appetite suppression, nausea, sleep disturbance, and decreased blood pressure and heart rate; rebound if not weaned
Irritability and severe disruptive behaviorAtypical (second generation) antipsychotics (aripiprazole, risperidone)595608Medication most effective if combined with behavioral strategies addressing identified environmental causes for the behavior and developing more appropriate responses for the child
• Vocal and motoric outbursts of anger, frustration, and distressDB/PCs strong support for 2 second-generation atypical antipsychotic medications (risperidone and aripiprazole) for reducing irritability, stereotyped or repetitive movements, self-injury, and hyperactivity
• Acts of aggression, self-injury, property destruction• Risperidone and aripiprazole are currently the only medications with FDA-approved labeling specific to irritability in ASD
• Behaviors referred to by caregivers as “agitation,” “tantrums,” “meltdowns,” or “rages”Adverse effects and monitoring:
• Common adverse effects include wt gain and dyslipidemia
• Monitoring: periodic assessment for extrapyramidal symptoms; measurement of wt, height, and BMI; and laboratory monitoring of glucose and lipid levels
• Metformin might be a useful treatment to help control wt gain.609
Other agents in this class, such as olanzapine and quetiapine, may have utility on the basis of their adverse effect profiles but do not have current FDA package insert indication for use in children with ASD
α-2 adrenergic agonists (clonidine, guanfacine)591,610Small studies documenting beneficial effects on irritability; need larger trials; may have better adverse effect profiles than atypical antipsychotics
SSRIs (fluvoxamine, citalopram)611,612Few studies focused on irritability and/or aggression; some reporting improvement in irritability; insufficient evidence to advise practice
Anticonvulsant mood stabilizers (valproic acid and divalproex sodium)613618Small studies suggestive of improvement in irritability; need larger studies; a limited number of placebo-controlled studies either do not support or are inconclusive regarding anticonvulsant medication as a treatment of irritability in patients with ASD
Serotonin-norepinephrine reuptake inhibitor (venlafaxine)619Effect size of improvement associated with venlafaxine was small, and irritability was not the primary outcome measured
Repetitive behaviorAtypical (second generation) antipsychotics (aripiprazole, risperidone)595598,620Multiple DB/PCs documenting improvement in repetitive behavior; short-term treatment
• Stereotyped motor mannerismsCommon adverse effects include increased appetite, fatigue, drowsiness, dizziness, and drooling
• CompulsionsMore effective for targets of tantrums, aggression, and SIB
• Behavioral rigidity, insistence on samenessAnticonvulsants (valproic acid and divalproex sodium)613,621,622Modest improvement has been reported with divalproex sodium treatment
May have improvement with topiramate as a second agent with risperidone
Most antiseizure drugs have potential for sedation, cognitive adverse events
SSRI (fluoxetine, fluvoxamine)480,509,611,612,623627Studies to date have not revealed effectiveness of SSRI medications for repetitive behaviors related to ASD, although they may diminish anxiety
SSRIs may be effective for reducing symptoms of OCD and of anxiety when included in a comprehensive approach to treatment
Need comprehensive behavioral approaches to minimize repetitive behaviors
Anxiety, depressionSSRIs469,628Anxiety relief has been reported in trials of citalopram and buspirone, with fluvoxamine revealing some effect in female patients with ASD; documented utility in children and youth without ASD
α-adrenergic (clonidine, guanfacine)Hyperactivation is an adverse effect of SSRIs in children and youth with ASD that may result in stopping the medication
The anxiety disorders most amenable to treatment are generalized anxiety disorder, separation anxiety disorder, and social phobias
Atypical (second generation) antipsychotics469,620If a mood dysregulation disorder is identified, treatment with a mood stabilizer and/or a second-generation antipsychotic is recommended, although an SSRI may be used to treat comorbid anxiety, OCD, or depression; behavioral activation with hypomanic or manic switches has been reported
First-line treatment is a program of cognitive behavioral therapy to reduce symptoms472475
Few studies have examined the specific effects for these symptoms; clinicians may consider use of these agents; although SSRIs, SNRIs, and/or buspirone may be effective for the treatment of anxiety in children with ASD, they have not been rigorously evaluated for this purpose507,626,627,629,630
Medications to consider include sertraline, fluoxetine, citalopram, or escitalopram for symptoms of anxiety and α-2 agonists (eg, guanfacine and clonidine and β-blockers such as propranolol), which may be useful for anxiety-related physiologic symptoms and behavioral dysregulation, and a short-acting benzodiazepine, such as lorazepam, could be considered for event related anxiety
  • DB/PC, double-blind placebo-controlled trial; FDA, US Food and Drug Administration; SIB, self-injurious behavior; SNRI, selective norepinephrine reuptake inhibitor. Adapted from Riddle MA. Pediatric Psychopharmacology for Primary Care. 1st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2016.