What is the cause of shivering and shaking in a patient with bipolar 2 disorder, anxiety, and borderline personality disorder (BPD) after initiating Bupropion (Wellbutrin), while already taking Duloxetine (120mg/day) and Pregabalin (75mg twice daily, BID)?

From the Guidelines

Shivering or shaking after starting Wellbutrin (bupropion) while on duloxetine and pregabalin requires immediate medical attention, as it may indicate serotonin syndrome, a potentially life-threatening condition. The combination of these medications, including duloxetine 120mg daily and pregabalin 75mg twice daily for bipolar 2 disorder, anxiety, and borderline personality disorder (BPD), with the newly added Wellbutrin, may be causing an interaction or side effect that needs to be addressed [ 1 ].

Potential Causes and Risks

The symptoms of shivering or shaking could be related to the pharmacodynamic profile of the medications, particularly the effect of Wellbutrin on dopamine and norepinephrine neurotransmitters, which when combined with duloxetine (affecting serotonin and norepinephrine) can sometimes cause excessive stimulation of the nervous system. According to the clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders [ 1 ], combining serotonergic medications can trigger serotonin syndrome, characterized by mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity.

Management and Recommendations

To manage these symptoms, it is crucial to contact a healthcare provider immediately to report them. The doctor may recommend reducing the Wellbutrin dose, adjusting the timing of medications, or potentially discontinuing one medication depending on the severity of symptoms [ 1 ]. It is essential not to stop any medications abruptly without medical guidance. While awaiting medical advice, staying hydrated, avoiding caffeine, and temporarily reducing physical exertion may help manage symptoms.

Key Considerations

• Serotonin syndrome is a potentially serious condition that can occur when combining multiple medications affecting serotonin levels [ 1 ].
• Close monitoring for suicidality is recommended, especially in the first months of treatment and following dosage adjustments [ 1 ].
• Behavioral activation/agitation may occur early in treatment, with dose increases, or with concomitant administration of drugs that inhibit the metabolism of SSRIs [ 1 ].
• Educating patients and their guardians about potential side effects, including serotonin syndrome and behavioral activation, is crucial [ 1 ].

From the FDA Drug Label

Some people have had serious side effects while taking bupropion to help them quit smoking, including: New or worse mental health problems, such as changes in behavior or thinking, aggression, hostility, agitation, depression, or suicidal thoughts or actions

Tell your healthcare provider about all of your medical conditions and all the medicines you take. Do not take any other medicines while you are taking bupropion hydrochloride extended-release tablets (XL) unless your healthcare provider has said it is okay to take them

The patient is already taking duloxetine and pregabalin for bipolar 2 disorder, anxiety, and BPD. Since starting bupropion, the patient is experiencing shivering/shaking.

• The FDA drug label does not directly address shivering/shaking as a side effect of bupropion.
• However, it does mention that bupropion can cause new or worse mental health problems, such as agitation.
• It is recommended to consult the healthcare provider about the side effects of bupropion and to report any new or sudden changes in mood, behavior, thoughts, or feelings 2.

From the Research

Shivering/Shaking since starting Wellbutrin

• The patient is already taking duloxetine 120mg/day and pregabalin 75mg BID for bipolar 2 disorder, anxiety, and BPD.
• There is no direct evidence in the provided studies that links Wellbutrin to shivering or shaking in patients taking duloxetine and pregabalin.
• However, study 3 suggests that the combination of duloxetine and bupropion (another antidepressant) can be effective for treatment-resistant major depressive disorder, but it does not mention shivering or shaking as a side effect.
• Study 4 discusses potential drug-drug interactions between COVID-19 treatments and antidepressants, mood stabilizers, and benzodiazepines, but it does not provide information on interactions between Wellbutrin, duloxetine, and pregabalin that could cause shivering or shaking.
• Study 5 reviews the prevention of postoperative shivering, which is a different context, but it mentions that serotonergic pathways may play a role in the pathogenesis of shivering, and duloxetine is a serotonin-norepinephrine reuptake inhibitor.
• Study 6 discusses the uses and dangers of benzodiazepines, but it does not provide information on shivering or shaking as a side effect of benzodiazepines or other medications.
• Study 7 evaluates the efficacy and safety of combined bupropion and duloxetine for treatment-resistant atypical depression, but it does not mention shivering or shaking as a side effect.

Potential Interactions and Side Effects

• The patient's symptoms of shivering or shaking could be related to the addition of Wellbutrin to their medication regimen, but the exact cause is unclear based on the provided studies.
• It is possible that the combination of duloxetine, pregabalin, and Wellbutrin may be contributing to the patient's symptoms, but more information is needed to determine the cause.
• The patient's healthcare provider should be consulted to determine the best course of action and to rule out any potential interactions or side effects.