How Do Serotonin-Dopamine Activity Modulators (SDAMs) Work?

Serotonin-dopamine activity modulators (SDAMs) are medications prescribed for the treatment of psychiatric disorders such as schizophrenia and bipolar disorder. SDAMs improve psychiatric symptoms by modulating the activity of serotonin and dopamine, two neurotransmitters involved in the regulation of mood and emotions.

Neurotransmitters are chemicals that nerve cells (neurons) release to transmit nerve signals. Each neurotransmitter binds to specific types of receptors on neuronal membranes. Receptors are protein molecules that initiate downstream action within the cell in response to stimulation by the particular neurotransmitter.

Known as the "happy hormone," dopamine regulates the brain’s reward system and is responsible for the sensation of pleasure, in addition to other functions including movement, emotions and cognition. Serotonin plays a vital role in most systems in the body including regulation of sleep, digestion, cognition, mood and behavior.

SDAMs modulate serotonin and dopamine neurotransmission by enhancing the activity of inhibitory receptors and blocking excitatory receptors. Some SDAMs also have effects on other neurotransmitters such as norepinephrine, another neurotransmitter involved in mood, attention and energy.

Each SDAM works in unique ways that include the following:

• Act as a partial agonist at D2 dopamine receptors, which are excitatory, and 5-HT1A serotonin receptors, which are inhibitory. Partial agonists enhance or block receptor activity depending on the neurotransmitter concentration levels.
• Act as an antagonist at 5-HT2A serotonin receptors, which are excitatory. Antagonists block receptor activity, while agonists enhance receptor activity.
• Act as an antagonist at D2 and 5-HT2A receptors, both of which are believed to be involved in psychosis.

Some SDAMs are combined with opioid antagonists to mitigate their side effect of weight gain. Opioid antagonists bind to opioid receptors on certain neurons known as pro-opiomelanocortin (POMC), which prevents the feedback of hunger sensation from the body.

SDAMs are oral tablets or capsules used in the treatment of the following conditions:

• Schizophrenia
• Bipolar I disorder
• Major depressive disorder

Side effects of SDAMs may include the following:

• Somnolence (drowsiness)
• Sedation
• Increase in blood glucose levels
• Increase in HbA1c values
• Increase in triglyceride and/or cholesterol levels
• Increase in weight
• Increase in appetite
• Increase in waist circumference
• Headache
• Extrapyramidal symptoms, which are drug-induced movement disorders such as:
  • Akathisia (inability to stay still)
  • Dystonia (involuntary contraction of muscles, including neck and throat muscles)
  • Dyskinesia (uncontrolled erratic writhing movements)
  • Akinesia (inability to move muscles voluntarily)
  • Muscle stiffness
  • Neuroleptic malignant syndrome (rare, life-threatening reaction)
  • Parkinsonism (symptoms similar to Parkinson’s disease, a neuromuscular disease)
  • Tardive dyskinesia (dyskinesia from long-term use of SDAMs)
• Nasopharyngitis (inflammation of nose and throat)
• Nausea
• Vomiting
• Dyspepsia (indigestion)
• Constipation
• Diarrhea
• Dry mouth
• Fatigue
• Dizziness
• Lethargy
• Asthenia (weakness)
• Paresthesia (abnormal skin sensations)
• Tremor
• Falls
• Back pain
• Speech disorder
• Stuttering
• Anxiety
• Amnesia (memory loss)
• Schizophrenia
• Increased salivation
• Increase in liver enzymes
• Liver damage
• Jaundice
• Hepatitis (liver inflammation)
• Pancreatitis (inflammation of the pancreas)
• Elevated creatinine phosphokinase (CPK)
• Decrease in cortisol levels
• Increase in blood pressure
• Neutropenia (low count of neutrophils, a type of white blood cells)
• Increase in blood insulin levels
• Diabetic ketoacidosis (complication from diabetes that causes excessive blood acids known as ketones)
• Diabetic coma
• Weight loss
• Pathological gambling and other compulsive behaviors
• Hypersensitivity reactions such as:
  • Rash
  • Urticaria (hives)
  • Pruritus (itching)
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Anaphylaxis (severe allergic reaction)
  • Drug rash with eosinophilia and systemic symptoms (DRESS)
• Withdrawal symptoms from discontinuation of medication
• Priapism (persistent and painful erection)
• Restless leg syndrome
• Rhabdomyolysis (breakdown of skeletal muscle cells)
• Deep vein thrombosis (blood clot in the vein)
• Pulmonary embolism

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand name of SDAM drugs include:

• brexpiprazole
• Caplyta
• lumateperone
• Lybalvi
• olanzapine/samidorphan
• Rexulti