Rexulti (Brexpiprazole), is an atypical antipsychotic approved by the FDA for the treatment of schizophrenia and major depressive disorder (as an adjunct). The drug was engineered via collaboration between pharmaceutical companies Otsuka and Lundbeck and is considered the successor to Abilify (aripiprazole), a formerly top-selling antipsychotic medication with an expired patent. Although Rexulti is marketed as being an upgrade from Abilify and other antipsychotics in terms of effectiveness and tolerability, many users still experience unwanted Rexulti side effects and/or adverse reactions.
Rexulti Side Effects & Adverse Reactions (List of Possibilities)
Included below is a comprehensive list of side effects associated with Rexulti (brexpiprazole). Understand that side effects from Rexulti are often subject to significant individual variation, such that the: specific side effects, severity of each side effect, and total number of side effects that you experience will be unique to you; not everyone will have the same experience. Of all potential side effects that occur with Rexulti treatment, clinical trial data indicate that upper respiratory tract infection; akathisia; weight gain, and nasopharyngitis are most common.
Recommendation: If you ever have questions about specific Rexulti side effects or reactions that you’re experiencing, consult a medical professional – preferably a psychiatrist.
- Akathisia or restlessness: Although Rexulti was designed with the intention of minimizing akathisia, evidence suggests that akathisia is a very common side effect among Rexulti users. Akathisia is a movement disorder characterized by inner feelings of restlessness. Someone experiencing akathisia may have a difficult time sitting still such that they might fidget, move around more than usual, or appear jittery. Up to 6.6% of persons taking Rexulti in some clinical trials experienced akathisia (compared to just 3.2% of individuals taking a placebo).
- Anxiety: Though many people will report decreased anxiety while using Rexulti, others will experience increased anxiety. The increased anxiety may be due to the effect of Rexulti upon serotonin (particularly 5-HT1A) and/or dopamine (D2 and D3) receptors. Some people don’t react well to the drug’s modulation of serotonergic and dopaminergic transmission. Others may experience the paradoxical reaction of “relaxation-induced anxiety,” or possibly become more anxious due to slowed thought-speed or impaired cognitive function.
- Appetite increase: Rexulti users should not be surprised if they experience an increased appetite and/or food cravings as a side effect. It is understood that Rexulti causes significant weight gain in a subset of users, and a reason for this weight gain may be related to appetite stimulation. If your appetite increases while using Rexulti, you may need to carefully monitor your caloric intake to ensure that it isn’t excessive.
- Blood pressure changes: For some individuals, Rexulti can affect blood pressure. While high blood pressure is a possibility, low blood pressure is more likely as a side effect. If your blood pressure drops significantly and/or suddenly (e.g. via orthostatic hypotension), this could result in fainting. Anyone with a history of blood pressure abnormalities should regularly monitor their blood pressure while taking Rexulti. If you notice any major blood pressure changes during Rexulti treatment, be sure to inform your doctor as soon as possible.
- Body temperature dysregulation: The medication insert for Rexulti suggests that some individuals may experience body temperature dysregulation as a side effect. It was noted that increased body temperature (e.g. fever) may be more likely among Rexulti users who are: engaging in strenuous exercise; in extreme heat (outdoor or indoor); dehydrated; or using other medications like anticholinergics. If you notice a fever while taking Rexulti or feel as though your body temperature is abnormal, be sure to tell your doctor.
- Cognitive impairment: Due to the fact that Rexulti alters serotonergic and dopaminergic activity within the brain, there’s a chance that it may cause cognitive deficits and/or “brain fog” (i.e. unclear thinking). In other words, you may have a difficult time learning new information, remembering things (i.e. retrieving memories), or concentrating, focusing, and paying attention to things. In some cases, cognitive impairment will subside as your brain adapts to the effects of the drug. That said, you may need to work with your psychiatrist to adjust dosing and/or utilize other substances to enhance your cognitive performance if it seems impaired during treatment.
- Constipation: Certain Rexulti users will experience constipation as a side effect of treatment. The constipation may be due to the effect of Rexulti slowing the movement of food through the digestive tract. Another possibility is that constipation is associated with changes in gut bacteria as a result of Rexulti. If you’re constipated, ask your doctor whether it might be helpful to use an over-the-counter medication for constipation relief.
- Depression: Despite the fact that Rexulti is actually prescribed to treat depression (as an adjunct), it can sometimes cause depression in persons without a history of depression – or worsen depressive symptoms among individuals with a history of depression. If you become depressed or more depressed during Rexulti treatment, it is recommended to talk to a psychiatrist. It’s possible that the neurochemical effects exerted by Rexulti are not a good fit for your preexisting neurochemistry.
- Diarrhea: A side effect that some individuals struggle to manage during Rexulti treatment is diarrhea. Some individuals may benefit from Rexulti, but might end up with diarrhea so extreme, that they want to quit taking the medication. If you’re experiencing diarrhea, it is recommended to ask your doctor about over-the-counter antidiarrheal agents like Imodium. Sometimes taking Imodium completely mitigates the drug-induced diarrhea and allows patients to tolerate Rexulti.
- Dizziness: Rexulti users may report feeling dizzier than usual while taking the drug. Dizziness is a relatively common side effect, but usually isn’t severe. Furthermore, dizziness is usually most extreme in the early stages of treatment when the brain is first adapting to the drug. That said, if the dizziness seems severe and/or problematic, it is recommended to discuss it with your doctor. In some cases, dizziness might be a sign of low blood pressure, which may be a precursor to fainting.
- Dystonia: Dystonia is a side effect of Rexulti characterized by involuntary muscle contractions that cause repetitive movements. Some individuals with dystonia will exhibit frequent twisting movements or appear to have a spasm. Rexulti documentation indicates that dystonia usually is noticeable within the first few days of treatment at low doses. If you experience dystonia from Rexulti, inform your doctor immediately.
- Fatigue: While taking Rexulti, you may experience fatigue or low energy as a side effect. The fatigue may be related to decreased activity of stimulatory neurotransmitters in the brain. Most people will feel a bit more fatigued than usual while under the influence of Rexulti, but it’s usually not severe enough to interfere with their functioning. Moreover, fatigue may be most noticeable early in treatment and might gradually subside as a person adapts to the effect of Rexulti over a longer-term.
- Headaches: It is estimated that up to 7% of users taking Rexulti will experience headaches as a side effect. The headaches experienced as a side effect may vary among users in terms of frequency (how often they occur) and severity (intensity). Some people may experience very infrequent headaches of modest severity, whereas others might experience very frequent and severe headaches. If you experience severe headaches from Rexulti, it is recommended to inform your doctor and ask about how they can be managed.
- Heart rate changes: A small percentage of individuals will notice changes in their heart rate while taking Rexulti. It is usually more common for heart rate to slow down as opposed to speeding up. Heart rate changes may be due to altered activation of the peripheral nervous system (e.g. decreased sympathetic tone) or changes in blood pressure. If you notice that your heart rate has changed during treatment with Rexulti, do not hesitate to contact a medical professional and discuss this side effect.
- High blood sugar: It has been noted that Rexulti can trigger high blood sugar (hyperglycemia) in some users. High blood sugar is associated with ketoacidosis or hyperosmolar coma and death among persons using atypical antipsychotics. Because high blood sugar is a serious side effect, it should be treated as a medical emergency and reported immediately to a medical professional. To ensure that you don’t have high blood sugar from Rexulti, it is recommended to have your doctor assess fasting plasma glucose initially after the initiation Rexulti, as well as on a regular basis throughout long-term treatment.
- Insomnia: A side effect of Rexulti that occurs in a small percentage of users is insomnia. The insomnia may be related to changes in the activity of certain neurotransmitters and/or hormones throughout Rexulti treatment. Nighttime insomnia might also occur as a result of resting or sleeping too much during the day while taking Rexulti. If your insomnia doesn’t seem to improve after several weeks of treatment, let your doctor know. Perhaps something as simple as a dosing adjustment or adjunctive medication can help you manage the insomnia.
- Lightheadedness: Feeling lightheaded is something that can occur when taking Rexulti. If the lightheadedness isn’t too extreme and occurs in the early stages of treatment, it could be a result of the brain adjusting itself to Rexulti. However, if the lightheadedness is severe and/or persistent, there’s a chance that it’s related to blood pressure changes. If your blood pressure drops too low during treatment, you may feel lightheaded and could end up fainting. Always mention any lightheadedness that you are experiencing to a doctor.
- Motor impairment: According to official medication documentation, Rexulti has the potential to impair motor skills in users. For this reason, it is recommended to avoid driving, operating heavy machinery, or engaging in strenuous physical exercise until you know how Rexulti affects your motor function. In some cases, motor impairment occurs initially with new users (or after a dosage increase) and fades as the body adapts to Rexulti’s effect. In short, never engage in any activities until you’re 100% sure that your motor function isn’t compromised.
- Nasopharyngitis: It is estimated that up to 5% of Rexulti users will experience nasopharyngitis as a side effect. Nasopharyngitis refers to swelling of the nasal passages and the back of the throat. This may result in a host of symptoms that are analogous to those associated with the “common cold” such as: coughing, runny nose, sneezing, etc. In any regard, this side effect may be the reason that some individuals report Rexulti makes them feel sick.
- Nausea: Some individuals will experience nausea as a side effect of Rexulti. The nausea is usually modest and probably won’t be severe enough to provoke vomiting. Furthermore, most new users of Rexulti will notice that the nausea gradually declines as they adjust to the effects of Rexulti over a longer-term. That said, some individuals may end up vomiting as a result of extreme nausea during treatment. For this reason, nausea should always be reported to medical professionals during treatment as it may be a sign of a serious adverse reaction.
- Orthostatic hypotension & syncope: Rexulti and other antipsychotics can cause orthostatic hypotension (sudden drop in blood pressure when standing) and syncope (fainting). It is stated that the risk of orthostatic hypotension and syncope is greatest when initiating treatment and/or increasing a patient’s dose. If you notice decreased blood pressure or feel lightheaded and dizzy each time you stand upright, you may have orthostatic hypotension from Rexulti. Inform your doctor of this side effect as soon as it is noticed.
- Sleep changes: Many people will notice changes in their sleep patterns while using Rexulti. Some individuals will sleep considerably more than usual as a result of side effects like lethargy and somnolence, whereas others may sleep less than usual due to insomnia. If you find yourself sleeping at odd times or sleeping significantly more or less than usual, report this to your doctor.
- Sweating: Some Rexulti users have noted that the drug causes them to sweat significantly more than usual. Sweating may be related to changes in concentrations of certain hormones within the body, or dysregulation of body temperature (e.g. fever). If you’re sweating excessively, this could cause dehydration and/or electrolyte imbalances.
- Upper respiratory tract infection: One of the most common Rexulti side effects is upper respiratory tract infection. Evidence suggests that up to 6.9% of all users will experience an upper respiratory tract infection as a side effect of Rexulti. This means that Rexulti users may be more prone to certain viral infections than non-users. Signs of an upper respiratory tract infection include: sore throat, coughing, sneezing, and/or stuffy nose.
- Weight gain: In clinical trials, approximately 6.3% of Rexulti users experienced significant weight gain compared to just 0.8% of placebo users. Based on this finding, it is apparent that Rexulti can cause weight gain as a side effect. Weight gain may result from changes in basal metabolic rate, increased appetite (and caloric intake), decreased physical activity (as a result of drowsiness), and/or changes in gut bacteria. It is recommended that doctors monitor the body weight of patients at baseline to ensure that weight gain doesn’t become problematic as to endanger health.
Rexulti Adverse Reactions & Rare Effects (List)
Included below are rare and/or adverse reactions associated with Rexulti (brexpiprazole). If you or someone you know experiences any of the adverse reactions listed below, it is imperative that you seek emergency medical attention. Prior to treatment with Rexulti, you may want to familiarize yourself with all potential adverse reactions so that if they occur – you can identify them.
- Allergic reaction: Some individuals may be allergic to Rexulti (brexpiprazole) or its components. A Rexulti allergy may trigger an allergic reaction with symptoms such as: anaphylaxis, bodily swelling (face, lips, tongue, throat), difficulty breathing, hives (rash). Some individuals may also experience itchy skin, nausea, and/or vomiting as a result of an allergic reaction.
- Cerebrovascular events: Certain individuals may experience cerebrovascular events while taking Rexulti. It is known that related medications and atypical antipsychotics can increase one’s risk of stroke and transient ischemic attack. For this reason, anyone with a history of cerebrovascular events and/or medical conditions that increase risk of cerebrovascular events – should be carefully monitored if using Rexulti.
- Difficulty swallowing (Dysphagia): A small percentage of Rexulti users may experience dysphagia, or difficulty swallowing, as an adverse reaction to the medication. The dysphagia may be accompanied by esophageal dysmotility or irregular contractions in the esophagus, as well as aspiration or difficulty breathing. Persons with a history of aspiration are at increased risk of experiencing dysphagia while taking Rexulti.
- Dyslipidemia: A subset of patients taking Rexulti may exhibit dyslipidemia as an adverse reaction. Dyslipidemia refers to abnormalities in concentrations of plasma cholesterol, triglycerides, or both. Because unfavorable changes in plasma cholesterol and/or triglycerides increase one’s risk of atherosclerosis and other cardiovascular conditions, it is recommended to carefully monitor lipids regularly during Rexulti treatment.
- Fainting & Falling: It is known that antipsychotics can cause somnolence, orthostatic hypotension, motor impairment, and sensory instability – each of which might increase one’s risk of fainting and/or falling throughout treatment. Fainting and falling may result in fractures (broken bones) and other serious injuries. Individuals with preexisting medical conditions and/or using other medications that also increase risk of fainting or falling – may be at highest risk of fainting and/or falling during Rexulti treatment.
- Leukopenia, neutropenia, agranulocytosis: Using antipsychotics like Rexulti may cause leukopenia, neutropenia, or agranulocytosis. These are specific conditions in which the counts of blood cells significantly change and increase one’s risk of death. For this reason, Rexulti users should receive regular blood work to ensure that their complete blood count, white blood cell count, neutrophil count, etc. – stay within normal ranges. Rexulti should be discontinued at the first sign of abnormal blood work.
- Neuroleptic Malignant Syndrome (NMS): Neuroleptic malignant syndrome is a potentially-fatal adverse reaction to antipsychotic drugs like Rexulti. Signs of neuroleptic malignant syndrome include: altered mental status, autonomic instability (e.g. dizziness, heart rate changes, etc.), disorientation, fever, and muscle rigidity. Other signs of neuroleptic malignant syndrome include: creatinine phosphokinase, rhabdomyolysis, and renal failure. If neuroleptic malignant syndrome is suspected, Rexulti needs to be discontinued immediately and the patient needs to undergo treatment plus monitoring.
- Seizures: Rexulti may trigger seizures as an adverse reaction in a subset of users. For this reason, anyone with a history of seizures or medical conditions that increase odds of a seizure should use Rexulti with caution. If seizures occur, Rexulti will likely necessitate discontinuation.
- Suicidal thoughts: Even though Rexulti can effectively treat depression as an adjunct, not everyone experiences a mood boost from the drug. Some individuals will experience increased depression and suicidal thoughts as a side effect. If you end up experiencing suicidal thoughts while taking Rexulti, you’ll need to seek emergency medical attention. Suicidal thoughts likely indicate that Rexulti is not compatible with your specific neurochemistry.
- Tardive Dyskinesia (TD): Rexulti may cause tardive dyskinesia in a small number of users. Tardive dyskinesia is a potentially-irreversible condition characterized by involuntary repetitive body movements. Some people with tardive dyskinesia experience uncontrollable facial jerks. Risk of tardive dyskinesia is increased among persons who use Rexulti for a long-term and/or at high doses. That said, even low-dose and short-term users can develop this adverse reaction. If tardive dyskinesia occurs, Rexulti may warrant discontinuation.
- Vomiting: Rexulti may cause gastrointestinal distress and nausea, each of which might induce vomiting. Rexulti may also trigger an allergic reaction which might cause you to vomit. In new users, the vomiting may subside as the body adapts to the effects of Rexulti over a long-term. However, because vomiting might be indicative of a more serious reaction to Rexulti, it should be reported immediately to a medical doctor.
Note: The above list of Rexulti side effects and adverse reactions may be incomplete. If you know of additional side effects that were not mentioned in this article, be sure to report them in the comments section.
- Source: https://rexultihcp.com/
- Source: https://www.otsuka-us.com/media/static/Rexulti-PI.pdf
Variables that influence Rexulti side effects
There are a multitude of variables that can influence the specific Rexulti side effects that you experience, as well as their severities. These influential variables include: Rexulti dose, duration of treatment, use of other substances (e.g. medications), and individual factors (e.g. genetics). In most cases, a combination of these variables will explain why some individuals experience more numerous and/or severe Rexulti side effects compared to others.
Rexulti dose (High vs. Low)
The dosage of Rexulti that you take may influence the number and/or severity of side effects that you experience. In general, side effects tend to be more numerous and severe among persons using high doses of Rexulti, compared to lower doses. Furthermore, some side effects may only occur in certain users when high doses of Rexulti are administered, but not at lower doses.
Medication insert data indicate that Rexulti is recommended to be administered at dosages between 2 mg and 4 mg per day for the treatment of schizophrenia, and between 2 mg and 3 mg per day for the treatment of major depressive disorder. Most individuals will have less severe side effects at lower doses than at higher doses. This is because at higher doses, Rexulti alters physiological homeostasis to a greater extent than at lower doses.
Duration of Rexulti use (Short vs. Long-Term)
The duration over which you’ve been using Rexulti may also determine how severe your side effects end up. Over the short-term, many individuals will experience side effects associated with their brain and/or body adapting to the drug. Many of these short-term side effects tend to dissipate as the brain and/or body finally adapt to the effect of the drug over a longer-term of treatment.
However, even though adaptation-related side effects can resolve with longer-term use of Rexulti, new side effects can emerge throughout treatment. Long-term use is associated with dosing increases, as well as long-term physiologic changes that might increase risk of certain side effects like tardive dyskinesia or neuroleptic malignant syndrome. In sum, you may notice changes in your side effects in accordance with how long you’ve used Rexulti.
Use of other substances with Rexulti
It is known that using other substances, whether it be medications, illicit drugs, or supplements – can influence the side effects that you experience from Rexulti. Some substances may exacerbate side effects from Rexulti or cause interaction effects, whereas others may attenuate side effects of Rexulti – and make it easier to tolerate. It is thought that concurrent use of substances that interact with hepatic enzymes CYP3A4 and/or CYP2D6 may increase likelihood of Rexulti side effects.
Specifically, any substances that are CYP3A4 inhibitors, CYP2D6 inhibitors, or CYP3A4 inducers – could alter the hepatic metabolism of Rexulti and potentiate its side effects. Moreover, even if a medication doesn’t interact with the hepatic metabolism of Rexulti, it may modulate its neurochemical effects within the brain to bolster or attenuate certain side effects. For this reason, you should be cognizant of the fact that using other substances with Rexulti might explain some of the side effects that you experience.
Individual factors (Specific Rexulti user)
A host of individual factors such as a person’s genetics, preexisting medical conditions, and lifestyle – can also influence Rexulti side effects. Someone with certain genes, no medical conditions, and a relatively healthy lifestyle may have fewer side effects than an individual with other genes, several medical conditions, and an unhealthy lifestyle.
- Administration specifics: For some individuals the time of day at which Rexulti is administered, as well as whether it is taken with food – might influence their side effects. Though administration specifics such as time of day and empty vs. full stomach don’t always influence side effects, these should be considered as potential influencers.
- Genetics: Having certain genes may determine how well you’re able to tolerate Rexulti. Genes involved in encoding for CYP450 enzymes such as: CYP3A4 and CYP2D6 maybe especially important influencers of Rexulti side effects. Variants in allelic expression of CYP3A4 and/or CYP2D6 could significantly increase likelihood of severe side effects. Expressing certain genes involved in the regulation of monoamine levels may also increase likelihood of certain side effects – compared to expressing other genes.
- Lifestyle (diet, sleep, stress): A person’s dietary choices, sleep quality, and stress levels may increase or decrease likelihood of Rexulti side effects. For example, someone who is eating a poor diet and/or is deficient in key nutrients or someone who isn’t getting a good night’s sleep – may experience more intense side effects as a result of these lifestyle factors. On the other hand, someone who keeps stress low, is getting enough sleep each night, and is eating a balanced diet – may find it easier to manage Rexulti side effects.
- Medical conditions: The specific medical conditions for which a person is using Rexulti may increase the likelihood of certain side effects based on the underlying neurochemistry associated with the condition. Moreover, other medical conditions such as cerebrovascular conditions, diabetes, and/or hyperlipidemia might increase likelihood of adverse reactions on Rexulti. Always evaluate your current medical diagnoses and consider how they might influence Rexulti side effects.
Rexulti (Brexpiprazole): Do the benefits outweigh the side effects?
If you’re using Rexulti, you should regularly evaluate whether the therapeutic benefits associated with treatment outweigh its negative or unwanted side effects. The majority of users will experience very modest, but tolerable side effects and significant therapeutic benefit. In fact, some individuals may experience no problematic side effects with marked symptomatic improvement.
In this case, the benefits would clearly be outweighing the side effects and treatment continuation would be warranted. On the other hand, if side effects are interfering with aspects of your life and/or are endangering your health, you may need to discontinue Rexulti – regardless of whether it was beneficial. It doesn’t really make much sense to continue a medication with side effects that are jeopardizing your health.
For those who are having trouble deciding whether Rexulti is beneficial, it may be smart to document how you feel in a daily journal throughout treatment. By documenting how you feel each day while taking Rexulti, you’ll be able to look back after a month or so of treatment and know whether the drug seems to be working or ineffective. Moreover, you’ll also have documentation of each side effect that you experienced; this will make it easier to report to your psychiatrist.
Possible ways to reduce Rexulti side effects
Listed below are some strategies that may prove useful for reducing the number of and/or the severity of Rexulti side effects. Understand that the effectiveness of these strategies will be subject to significant individual variation. Moreover, know that you should never implement any of these side effect mitigation strategies without first consulting a psychiatrist to ensure that they’re safe.
- Dosage reduction: It is known that high doses of Rexulti can increase the severity and/or number of side effects. If you’re experiencing debilitating side effects, you may want to ask your doctor about reducing the dosage. The goal should be to take the “minimal effective dose” or lowest possible amount needed to control symptoms – as this will minimize odds of side effects.
- Concurrent substance use: If certain side effects are problematic, it may be smart to treat the most problematic side effects with the use of other substances. For example, if you’re experiencing diarrhea while taking Rexulti, you may want to target the diarrhea with Imodium. Talk to your doctor to determine whether it may be a good idea to administer other substances for the sake of reducing your most problematic Rexulti side effects.
- Modify administration: Though not usually effective, some have reported fewer side effects from modifying their administration details. This might mean taking Rexulti earlier or later in the day (modifying the timing) and/or taking Rexulti with more or less food than before.
- Stop using unnecessary substances: If you’re using other medically-unnecessary substances with Rexulti, you’ll want to stop taking these substances if you’re experiencing side effects. Some substances can interact with Rexulti and/or may cause interaction effects, and by stopping usage of unnecessary substances, you’ll decrease odds of an interaction effect.
- Continue using: Sometimes individuals will experience side effects in the early stages of Rexulti treatment that fade with continued usage. If you are a newer Rexulti user, it may be necessary to continue taking the drug over a longer-term in order for side effects to diminish.
Have you experienced Rexulti side effects?
If you’ve experienced side effects while taking Rexulti, mention them in the comments section below. To help others better understand your situation, provide some details including: your Rexulti dosage, whether you are using any other medications or substances (in addition to Rexulti), and your CYP450 genetics (specifically CYP3A4 and CYP2D6 expression). For example, you might be on a 3 mg dose, using an SSRI with Rexulti, plus be a CYP3A4 extensive metabolizer.
Also note how long you’ve been using Rexulti and whether you’ve figured out any ways to decrease the severity of certain side effects. Overall, you should know that no antipsychotic medication is perfect – most will have some side effects. Always work closely with your psychiatrist to determine whether Rexulti side effects are manageable – or if you might be better suited trying a different medication.