Apomorphine for Autism Spectrum Disorder

November 10th, 2022
Racelyn Lawas
Pharm.D. Candidate 2023
Jefferson College of Pharmacy

WHAT IS ASD?

Autism Spectrum Disorder (ASD) is a neurodevelopmental disease characterized by social interaction impairment, social communication impairment, and restricted interests/activities and repetitive behavior. Symptoms of ASD may show as early as 12 months of age, but for some, it may not show until 24 months of age or later. As children with ASD begin to reach adolescence and young adulthood, it may become more difficult for them to develop and maintain friendships, communicate with others, or understand the expected behavior at school. Due to their differences in brain function, it is important to be mindful of the signs and symptoms of ASD:

Social interaction and communication impairment:

• Avoids or does not maintain eye contact
• Does not respond to name by 9 months of age
• Uses a few or no gestures by 12 months of age (i.e. does not wave goodbye)
• Does not notice when others are hurt or upset by 24 months of age

Restricted interests and repetitive behavior impairment:

• Repeats words or phrases over and over
• Gets upset by minor changes
• Rocks body or spins in circles
• Must follow certain routines

Other characteristics

• Delayed movement and/or language skills
• Hyperactive or impulsive behavior
• Unusual mood or emotional reactions

It could be challenging to diagnose children with ASD as some may not at all show any of these symptoms. In addition, diagnosing does not involve blood work or medical testing. It is based on the patients’ behavior and developmental history.

ROLE OF DOPAMINE

Dopamine (DA) is the “reward center” of the brain and it plays a role in various body functions such as movement, memory, attention, behavior, and so on. Dopamine signals are transported via the Dopamine Transporter (DAT) which allows the reward center to function properly. It has been found that disruptions in the DA-DAT system are seen in people with ASD.

TREATMENTS FOR ASD

Symptoms of ASD generally involve deficits in speech, behavior, and social skills, therefore, the first-line treatment is behavioral therapy. However, medications are sometimes added to behavioral therapy to help patients function daily. Medications are chosen based on the targeted symptom(s).

Irritability and aggression: risperidone, aripiprazole, clozapine, haloperidol, sertraline
Aberrant social behavior: risperidone, haloperidol, oxytocin, secretin
Hyperactivity and inattention: methylphenidate, venlafaxine
Repetitive behavior: fluoxetine, citalopram, bumetanide
Cognitive disorder: memantine, rivastigmine
Insomnia: mirtazapine, melatonin

APOMORPHINE

Despite the amount of medications used to treat ASD symptoms today, there’s still ongoing research on ASD and how symptoms could be better improved. There is ongoing research of another medication called Apomorphine that is currently being prescribed to patients with Parkinson’s Disease to help control tremors. Apomorphine stimulates dopamine receptors which results in behavioral effects that are beneficial for patients with ASD. It is also used by veterinarians to target various symptoms similar to those with ASD, such as running in circles or repetitive behavior seen in cats and dogs. Although apomorphine has been observed to treat movement disorders since the 1870s, it remains as an off-label use to treat ASD symptoms.

WHERE TO GET APOMORPHINE

Apomorphine is currently available in the market as a subcutaneous injection and a sublingual film. It is not commercially formulated in any other oral form. However, here at CareFirst Specialty Pharmacy, Apomorphine can be specially compounded into sublingual troches/lozenges. The oral formulation is beneficial for patients who are unable to receive injection or intravenous formulations. In addition, it provides convenience and ease of administration without having to puncture the skin.

References:

1. Auffret M, Drapier S, Vérin M. The Many Faces of Apomorphine: Lessons from the past and challenges for the future. Drugs R D. 2018;18(2):91-107. doi:10.1007/s40268-018-0230-3
2. Chao OY, Pathak SS, Zhang H, et al. Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism. Mol Brain. 2020;13(1):111. doi:10.1186/s13041-020-00649-7
3. DiCarlo GE, Aguilar JI, Matthies HJG, et al. Autism-linked dopamine transporter mutation alters striatal dopamine neurotransmission and dopamine-dependent behaviors. J of Clin Inves. 2019;129(8):3407-3419. doi:10.1172/jci127411
4. Kim H, Lim C-S, Kaang B-K. Neuronal mechanisms and circuits underlying repetitive behaviors in mouse models of autism spectrum disorder. Behav Brain Funct. 2016;12(1). doi:10.1186/s12993-016-0087-y
5. LeClerc S, Easley D. Pharmacological therapies for autism spectrum disorder: a review. P T. 2015;40(6):389-397.