An 18 year old female comes into your  pharmacy today and says she has gained nearly 10 pounds after starting her new medications. She has not had any recent changes in diet or exercise. She recently saw her psychiatrist and was starting on medications for seizure disorder, depression and bipolar disorder. After looking at her profile you notice she was started on Topamax 50 mg daily, Elavil 25 mg daily, Zyprexa 10 mg daily and Wellbutrin 100 mg twice daily. Which of the following medications could be contributing to her unintentional weight gain? Select all that apply.

A. Topamax

B. Elavil

C. Zyprexa

D. Wellbutrin

E. None of the above cause weight gain

The correct answers are B and C.

Topamax, or topiramate, is an anticonvulsant used for the treatment of focal and generalized onset seizures as monotherapy or as adjunctive therapy. While the mechanism of action is not completely understood, it may be due to a combination of mechanisms including blockage of neuronal voltage-dependent sodium channels, GABA agonism, AMPA/kainite glutamate antagonism, and by weakly inhibiting carbonic anhydrase. Common side effects include drowsiness, paresthesia, and weight loss, making answer A incorrect.

Elavil, or amitriptyline, is a tricyclic antidepressant (TCA) used to treat major depressive disorder. Amitriptyline increases synaptic concentrations of serotonin and/or norepinephrine in the central nervous system by inhibiting the reuptake by presynaptic neuronal membrane pumps. Common side effects include hypertension, tachycardia, anxiety, and weight gain, making answer B correct. Other TCAs such as clomipramine, doxepin and imipramine are also associated with significant weight gain.

Zyprexa, or olanzapine, is an atypical antipsychotic that can be used for agitation and aggression associated with psychiatric disorders such as schizophrenia and bipolar disorder. Olanzapine is a potent antagonist of serotonin 5-HT_2A and 5-HT_2C, dopamine D_1-4, histamine H₁, and alpha₁-adrenergic receptors. It also exhibits moderate antagonism of 5-HT₃ and muscarinic M_1-5 receptors. The effect on dopamine and serotonin are suspected to give olanzapine it’s efficacy in schizophrenic and bipolar patients. Common side effects include orthostatic hypotension, constipation, increased appetite and weight gain, making answer C correct.

Wellbutrin, or bupropion, is an antidepressant that can be used for the treatment of major depressive disorder. It’s mechanism of action is not well understood and is structurally different from all other marketed antidepressants. It has some effects as a weak inhibitor of the neuronal uptake of norepinephrine and dopamine which are thought to contribute to its efficacy in major depressive disorder. Common side effects include tachycardia, insomnia, headache, agitation, and weight loss, making answer D incorrect.

Many medications used can have significant effects on weight and it is important to review medications that could be contributing to weight gain/loss if a patient is experiencing significant weight fluctuations that are unintentional and unexplained by lifestyle modifications. Antipsychotics, antidepressants, antiepileptics, and diabetic medications are commonly associated with weight gain.

Atypical antipsychotics such as clozapine and olanzapine are associated with the most weight gain and lithium is associated with moderate weight gain. Tricyclic antidepressants are associated with significant weight gain. SSRIs such as fluoxetine and sertraline have shown some weight loss with short-term use but long-term use has been associated with weight gain. Antiepileptics such as valproate and carbamazepine have been shown to cause weight gain while topiramate has been demonstrated to cause weight loss. For antihyperglycemics, insulin and sulfonylureas are associated with modest weight gain. Thiazolidinediones such as pioglitazone and rosiglitazone are also associated with weight gain which is thought to be due to fluid retention and/or fat redistribution. GLP-1 agonists, such as Victoza (liraglutide), and SGLT2 inhibitors, such as Farxiga (dapagliflozin), have been associated with significant weight loss. Saxenda, which uses a higher dose of liraglutide (3mg SQ daily as opposed to 1.8mg SQ daily), is FDA-approved for weight management in conjunction with lifestyle modifications.

Have a great week everyone! Let the promising news of a COVID-19 vaccine motivate you more to study in preparation for the NAPLEX which is just around the corner!

Dr. B