Preliminary Investigation of Lithium for Mood Disorder Symptoms in Children with Autism Spectrum Disorder

Background:  Children with Autism Spectrum Disorder (ASD) have higher rates of co-morbid psychiatric illness, including  mood disorders, than the general child population (Leyfer, 2006).  Numerous medications have been studied in individuals with ASD, yet only risperidone and aripiprazole (both atypical antipsychotics) have established evidence of efficacy, both for the treatment of irritability (Siegel, 2012).  While many children with ASD may experience irritability (aggression, self-injury and tantrums), a small portion also experience symptoms that are typical of a mood disorder, such as euphoria/elevated mood, mania, hyper-sexuality, paranoia or decreased need for sleep. Despite lithium’s established efficacy in controlling mood symptoms in the neuro-typical population, lithium has been almost unstudied in children with ASD.

Objectives:  The primary objective of the current study was to describe a subset of children with ASD who received lithium in order to assess potential target symptoms, safety and tolerability.  The secondary objective was to examine the relationship between mood disorder symptoms and clinician-rated global improvement scores.

Methods:  A retrospective chart review of thirty children diagnosed with ASD by DSM-IV TR criteria and prescribed lithium was conducted at two specialized inpatient psychiatry units.  Data included demographics, verbal ability, symptoms prior to lithium treatment, treatment duration and lithium blood levels. Clinical Global Impression of Improvement (CGI-I) ratings were performed by two board certified child psychiatrists with expertise in ASD (MS, CB). CGI-I scores were categorized into either “improved” (CGI-I score of 1 or 2) or “not improved” (CGI-I score ≥3). Data were systematically abstracted by research assistants at each site and sent to the primary site for analysis. The study was approved by the Institutional Review Boards of Maine Medical Center and Children’s Hospital Colorado.

Results:  Patients were an average of 13.6 (SD=4.1) years old, and primarily male (76.7%), Caucasian (96.7%), and Non-Hispanic (93.3%).  All 30 patients were diagnosed with ASD, 10% had a seizure disorder, 56.7% had intellectual disability, and 76.7% were verbally fluent.   The mean lithium blood level was 0.70 mEq/L (SD=0.26, Range=0.30-1.20) and the average length of lithium treatment was 29.7 days (SD=23.9, range=4-92). Forty-three percent of of patients were rated as improved on the CGI-I.  Independent t-tests indicated that patients who had improved on the CGI-I had a higher number of mood disorder symptoms (M=1.38, SD=1.26) than those who were not improved (M=0.57, SD=0.76), t=-2.01, p=0.058.  The presence of mania or euphoria/elevated mood were the symptoms most closely associated with a CGI-I improved rating, but were non-significant, p=0.06 and p=0.088 respectively.  Forty-seven percent of patients were reported to have “any” side effect, the most common of which were vomiting (13%), tremor (10%), fatigue (10%), irritability (7%) and enuresis (7%). 

Conclusions:  This preliminary exploration of lithium in children with ASD suggests that lithium may be a medication of interest for those who exhibit two or more mood disorder symptoms, particularly mania or euphoria/elevated mood.  A relatively high side effect rate merits caution.  These results are limited by the retrospective, uncontrolled study design.  Future study of lithium in a prospective trial with treatment sensitive outcome measures may be indicated.