Clinical Vignettes from Dr. Elizabeth Stuller
Dr. Elizabeth Stuller, a staff psychiatrist at the Amen clinics in Washington, DC and CEO of private practice Stuller Resettings in Baltimore, MD, provided this editor (Robert M. Post) with several interesting anecdotal observations based on her wide clinical experience with difficult-to-treat mood disordered patients.
- Stuller has used low-dose asenapine (Saphris), e.g. half a pill placed under the tongue, for depressed patients with alcohol use problems who have trouble getting to sleep. She has also used asenapine for rapid calming of agitated patients in her office.
- Stuller has also had success with the use of the atypical antipsychotic drug brexpiprazole (Rexulti) for patients with bipolar depression and low energy. She typically uses 0.5 mg/day for women and 1 mg/day for men. Stuller finds that there is little weight gain or akathisia with brexpiprazole.
- She has had success with the drug Nuedexta, which is a combination of dextromethorphan and quinidine and is approved for the treatment of sudden uncontrollable bouts of laughing or crying, known as pseudobulbar affect, which can occur as a result of neurological conditions or brain injuries. It is a combination of an NMDA antagonist and a sigma receptor agonist. Stuller starts with the 20mg dextromethorphan/10 mg quinidine dose once a day and increases to twice a day in week two. She finds it useful for behavioral effects of traumatic brain injury (TBI), anxiety resulting from the use of synthetic marijuana (sometimes called spice), and psychosis not otherwise specified. Stuller also finds that some patients appear to respond well to Nuedextra but not minocycline, or vice versa.
Editor’s Note: Note that these are preliminary clinical anecdotes conveyed in a personal communication, and have not been studied in clinical trials, thus should not be relied upon in the making of medical decisions. All decisions about treatment are the responsibility of a treating physician.
Dopamine Partial Agonists: An Overview
Several atypical antipsychotic drugs are partial agonists of dopamine. They provide weak stimulation of dopamine receptors in the brain and prevent dopamine from overstimulating the receptors by binding to them in its place.
In contrast, most antipsychotic and antimanic drugs are dopamine antagonists, which also bind to dopamine receptors but prevent any stimulation from occurring there.
A. Aripiprazole (Abilify) was the first partial dopamine agonist approved by the Food and Drug Administration for the treatment of schizophrenia, and mania, and as an add-on treatment to antidepressants for the treatment of unipolar depression, but not bipolar depression.
B. Brexpiprazole (Rexulti) received FDA approval for the treatment of schizophrenia and as an add-on treatment to antidepressants for the treatment of unipolar depression in 2015. It is similar to aripiprazole but has weaker activity at the dopamine D2 receptor. Brexpiprazole is associated with small increases in the hormone prolactin, as opposed to the small decreases in prolactin seen with aripiprazole.
C. Cariprazine (Vraylar) is FDA-approved for schizophrenia and mania, and it also has positive placebo-controlled data in bipolar depression and as an adjunct to antidepressants in unipolar depression. It differs from the others in that it is more potent at dopamine D3 receptors than at D2 receptors. It is thought that effects on D3 receptors may provide better antidepressant effects, but this proposition has not yet been tested.
New Atypical Antipsychotic Drug Brexpiprazole Improves Depression When Added to Antidepressants
Two studies published in the Journal of Clinical Psychiatry in 2015 suggest that the new atypical antipsychotic brexpiprazole (trade name Rexulti) safely improves depression when added to antidepressant treatment. The 6-week studies, both by Michael E. Thase and colleagues, compared brexpiprazole to placebo in people who had not responded adequately to one to three antidepressants and were taking at least one antidepressant at the time of the study.
The studies examined the effectiveness of different doses of brexpiprazole. Doses of 2mg/day and 3mg/day were more effective than placebo, while a dose of 1mg/day was not. The drug was well-tolerated by patients at each of these doses, although those taking the 3mg/day reported more side effects than those taking 2mg/day. The side effects included restless legs, weight gain, and headaches.
Like the atypical antipsychotic aripiprazole (Abilify), brexpiprazole partially blocks and partially stimulates dopamine receptors. While aripiprazole allows 61% activity at dopamine D2 receptors, brexpiprazole allows 43%. It is not yet clear how the new drug’s effects may differ from those of aripiprazole.
Another relatively new atypical antipsychotic drug, cariprazine (Vraylar) is approved by the Food and Drug Administration for schizophrenia and mania, but not yet for bipolar depression or as an add-on treatment to antidepressants in unipolar depression, although there are placebo-controlled trials showing that cariprazine can also treat these conditions.
Like aripiprazole and brexpiprazole, cariprazine also partially blocks and partially stimulates dopamine receptors. Unlike them, cariprazine is more potent at dopamine D3 receptors, which are linked to mood, motivation, and drug reward, than at D2 receptors, which are linked to motor control. It is not yet clear how these differences may change treatment outcomes or side effects.
