Abilify Side Effects (aripiprazole), Drug Interactions, Weighing Risks to Benefits

Alternative to Meds Editorial Team
Medically Reviewed by ATMC Clinical Review Team

Abilify Side Effects Summary

Abilify (generic aripiprazole) is an antipsychotic medication that comes in various formats. It is available as an oral tablet, a disintegrating oral tablet, an oral solution, and an intramuscular injectable and extended-release injectable form. While Abilify may have been the most correct choice during a crisis (see Indications and notes on usage below), all of these versions are subject to a number of potential Abilify side effects, significant adverse reactions, and possible safety concerns you can find below. The summary was derived from the FDA-approved drug label, the black box warnings on the packaging, and other sources, where indicated. A review of several clinical trials showed that the side effects of Abilify are more intense with higher dosage, and can also worsen with the length of time the drug is taken.^1,2

The most common Abilify side effects (between 5% – 10% or greater) can include:

• Impaired cognitive and motor function
• Weight gain (up to 28%)
• Changes in appetite
• Anxiety
• Akathisia (up to 16%)
• Restlessness
• Sedation, somnolence, fatigue, lethargy (14% up to 18%)
• Extrapyramidal disorders
• Tremor
• Nausea, vomiting
• Blurred vision
• Excess salivation, drooling
• Dizziness
• Increased frequency of colds in children
• Pyrexia
• Headaches
• Fever
• Constipation
• Insomnia (up to 17%)

Other severe side effects can include:

• Increase in suicidality (thoughts/behavior) in the elderly
• Increase in suicidality (thoughts/behavior) in children and young adult patients
• Increased mortality for elderly dementia patients or patients with dementia-related psychosis
• Infants are subject to extrapyramidal disorders when exposed to Abilify in the 3rd trimester
• Increased risk of stroke or other cardiac adverse events, including fatalities
• Seizures/convulsions
• NMS (neuroleptic malignant syndrome, see below for more information)
• Tardive Dyskinesia (see below for more information)
• Hyperglycemia/Diabetes Mellitus
• Pathological gambling
• Other compulsive behaviors
• Orthostatic hypotension (lowered blood pressure)
• Lowered white blood cell count

Antipsychotics are extremely heavy drugs, and may be required to meet the needs of a patient in severe crisis where sedation is necessary for their safety, or the safety of others.

However, the overprescribing of antipsychotics in general has come under scrutiny to ensure that each patient is properly prescribed and that the side effects of Abilify do not exceed an optimum risk-to-benefit ratio.

What is Abilify Prescribed to Treat?

Abilify in all forms except the intramuscular injectable version is approved for the following conditions:

• Schizophrenia
• Manic and acute mixed episodes in bipolar conditions
• As an adjunct treatment to antidepressants in major depressive disorder
• Irritability in autistic disorders
• Tourette’s disorder

The injectable intramuscular form of Abilify is only indicated for agitation in schizophrenia or agitation in bipolar mania.

How Does Abilify Work?

It has not been entirely established how Abilify works in terms of its mechanism of action. Because it has different properties compared to earlier drugs in its class, it is called a “3rd generation” antipsychotic. Typical antipsychotics are thought to block dopamine. Aripiprazole is thought to both block and enhance the transmission of certain neurotransmitters. Blocking the dopamine receptors would explain the sedating and erratic or manic thought-dampening side effects, and this may be more likely to occur at higher dosages. However, certain research theorizes that aripiprazole may also actually enhance or boost transmission of dopamine and/or other chemicals such as serotonin which some researchers think may explain its stimulating side effects on a significant percentage of people taking aripiprazole — such as insomnia, compulsive gambling behaviors, uncontrollable urges to shop or engage in sex, restlessness, and akathisia, for example.^9,10,12

Aripiprazole and Polypharmacy Side Effects

Many patients are diagnosed with “treatment-resistant depression,” meaning their Prozac or Cymbalta, etc., did not help. They are commonly prescribed aripiprazole to get a better result.

Persons diagnosed with ‘bipolar” who are taking lamotrigine also may find their condition not improved. These persons may be additionally prescribed aripiprazole to manage symptoms that are resistant to mono-drug therapy.

This now common and FDA-approved approach of polypharmacy has emerged, where doctors simultaneously prescribe multiple drugs, in similar or quite different drug classes, to get some sort of positive result. Drug interactions are another area of little understanding, but which may, at least in part, explain why some side effects of such polypharmacy produce not sedation but excitation, anxiety, worsened depression, suicidality, or a combination of side effects that seem to vary widely among individuals.¹¹

Side Effects of Concern from Drug Interactions with Abilify

• Antidepressants: Persons up to the age of 24 taking an antidepressant medication concurrently with Abilify may experience worsening of depression and increased suicidality, especially notable in the beginning phases of drug treatment. Other interactions may present akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.
• Lithium or Valproate: Adults taking Ability at the same time as lithium or valproate can experience akathisia, insomnia, and extrapyramidal symptoms.
• Heart medications: The safety of some heart medications in the adult population may be compromised by taking them alongside Abilify, which could exacerbate heart conditions.
• Lorazepam: Taking Abilify and this benzodiazepine together increases sedation effects and may also increase low blood pressure symptoms.

A note on genetic markers: Since many drugs are dependent for their mechanism of action on specific genetic markers, ensure your prescriber is aware of these potential interactions.

Abilify Side Effects over Long-Term Use

There has been a poverty of long-term studies on antipsychotics, and the available studies show inconsistent findings. We have observed some clinical research studies indicating that the intensity and number of Abilify side effects may increase with the dosage, and may lessen with lowered dosages.^1,2

We can also look to the 48-week study published in the British Journal of Psychiatry from 2016, showing that some antipsychotics had “less bad” outcomes than others for side effects.³

Research has shown a possible long-term outcome of antipsychotic medications in general, called “antipsychotic-induced dopamine supersensitivity.” This condition is associated with side effects such as tardive dyskinesia and other movement disorders, as well as rebound psychosis/mania when the antipsychotic medication is stopped too abruptly. Antipsychotics block the dopamine receptors to prevent psychotic presentations. But over time, these same receptors become highly sensitive, and this side effect may be intensified by the length of time the dopamine receptors remain blocked, or occupied, by the drug. For this reason, antipsychotic withdrawal or even dosage reduction must be done extremely, extremely slowly.^6,7

Is Recovery Possible Without Drug-Induced Side Effects?

Some of the most interesting studies ever conducted were those of 2-time Nobel Prize winner, Dr Linus Pauling, who presented his orthomolecular approach to treating schizophrenia in a hearing given to the 1977 Connecticut State Senate.⁴ It received mixed reactions, some absolutely critical, and some overwhelmingly positive, at the idea of using natural methods for therapy. Pauling’s use of vitamin C, niacin, and B vitamins in the treatment of schizophrenia was groundbreaking at the time. More can be found on his research, the results of his years-long studies, by even a cursory search at orthomolecular.org. 

Another pioneer in the work of treating mental illness in effective, yet non-harmful ways was Dr. Abram Hoffer. He notes in his article published in the 2009 Journal of Orthomolecular Medicine that patients at the time who were diagnosed with schizophrenia, and cured of that condition with nicotinic acid, were then re-diagnosed with another illness, pellagra, as their chronic schizophrenia symptoms had disappeared. Pellagra is a disease caused by a deficiency of niacin. But pellagra symptoms and those of schizophrenia are very much alike.⁵

In Finland, a novel treatment for schizophrenia using a heartburn drug called “famotidine” has generated much interest from the global medical community. Famotidine targets histamine receptors, not dopamine receptors. A small study of 30 schizophrenic participants was done over a period of 4 weeks. Half of the group was given a placebo, the other half famotidine at 200mg per day. After 4 weeks, there was a statistically significant reduction in schizophrenic symptoms in the famotidine group. The placebo group’s symptoms did not change at all. While more testing needs to be done, this marks another very positive direction in a long quest for treating mental illness without the liability of Abilify or other antipsychotic drug side effects.⁸

ATMCs: Alternative Treatment Approach vs Abilify Side Effects

We recognize that not everyone is a candidate for inpatient treatment where antipsychotic drug reduction or Abilify withdrawal is the end goal. For some, reducing dosage to the lowest amount possible while enjoying a good quality of life is a highly satisfactory goal.

Certainly, where a person has stabilized with the use of an antipsychotic medication, it may be possible to carefully reduce the dosage. And in some cases, total reduction has been achieved without relapse.

A human being is much more than a “sack of chemicals.” Nonetheless, lab testing can reveal some fixable signs of nutritional dysfunction and genetic biomarkers that may explain why a person’s symptoms emerged in the first place.

With the orderly use of orthomolecular approaches to reducing both original symptoms and Abilify side effects, combined with the use of effective holistic adjunctive therapies, it is possible to reach a satisfactory outcome that is precisely tailored to the individual’s needs. We encourage you to take an in-depth look at the wide range of services available at ATMC, which can be found at the above link.

We’ve helped many people who were desperate for solutions, whose prescriptions were just not helping. And their attempts to come off these medications were sometimes disastrous. We provide a safe, proven pathway to recovery and return to natural mental health. Please feel free to call us for more information that may help you in your quest for a better outcome for yourself or your loved one, to gain true freedom from Abilify side effects.

Timothy’s Successful Abilify Withdrawal

Excerpt:

“Every member of staff, from housecleaning to chefs to care professionals to doctors, exhibited a passion for what they were doing, which was helping each individual resident heal and overcome medication withdrawals. They are supportive any time of day or night. All of them expressed genuine care for each resident … and that care shined through each and every day of my care.

While at ATMC, I participated in so many different treatments geared towards removing latent medications from my system and in treatments that provided emotional support. There were spa-type treatments as well. Those included massages, acupuncture, toxin removing foot baths as well as relaxation inducing foot baths. There were several other toxin removing and healing related treatments also. There were many other effective treatment modalities while I was a resident at ATMC. I participated in cold plunges, meditation, yoga, additional exercises, group support sessions, art therapy, dance therapy, hikes, … an individualistic supplementation protocol that is tailored for each person based on their specific needs and symptoms … and many other program features.

[My therapist] was very willing to provide me with Christian-based therapy, which made me feel even more heard and cared for. My view on therapy has gone from regarding it as ineffective to seeing it as a strong form of treatment that should always be considered and tried before taking any psychiatric medications.

I [graduated] from the facility in a healthier state than I have been in for more than a decade, both physically and mentally.”

Read Timothy’s Full Successful Withdrawal from Abilify here.

for Help with Abilify Side Effects

Sources:

1. FDA Drug Label Abilify (aripiprazole) Tablets, Discmelt Orally Disintegrating Tablets, Oral Solution, Injection (for intramuscular use), and Abilify Maintena (for extended-release injectable suspension for intramuscular use) First approval 2002 [cited 2025 July 20]

2. Seshadri A, Wermers ME, Habermann TJ, Singh B. Long-term Efficacy and Tolerability of Adjunctive Aripiprazole for Major Depressive Disorder: Systematic Review and Meta-analysis. Prim Care Companion CNS Disord. 2021 Jun 24;23(4):20r02799. doi: 10.4088/PCC.20r02799. PMID: 34167174. [cited 2025 July 20]

3. Zhao YJ, Lin L, Teng M, Khoo AL, Soh LB, Furukawa TA, Baldessarini RJ, Lim BP, Sim K. Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials. BJPsych Open. 2016 Feb 5;2(1):59-66. doi: 10.1192/bjpo.bp.115.002576. PMID: 27703755; PMCID: PMC4995551. [cited 2025 July 20]

4. Pauling’s Study of Schizophrenia, published online N.D. [cited 2025 July 20]

5. Hoffer A Orthomolecular Treatment of Schizophrenia published in the 2009 Journal of Orthomolecular Medicine, Vol 24 No 3 & 4 (pdf) [cited 2025 July 20]

6. Nakata Y, Kanahara N, Iyo M. Dopamine supersensitivity psychosis in schizophrenia: Concepts and implications in clinical practice. J Psychopharmacol. 2017 Dec;31(12):1511-1518. doi: 10.1177/0269881117728428. Epub 2017 Sep 19. PMID: 28925317.[cited 2025 July 20]

7. Seeman P. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors. CNS Neurosci Ther. 2011 Apr;17(2):118-32. doi: 10.1111/j.1755-5949.2010.00162.x. PMID: 20560996; PMCID: PMC6493870.[cited 2025 July 20]

8. University of Helsinki New Treatment for Schizophrenia Discovered in Finland published online 1.7.2013 [cited 2025 July 20]

9. Davies MA, Sheffler DJ, Roth BL. Aripiprazole: a novel atypical antipsychotic drug with a uniquely robust pharmacology. CNS Drug Rev. 2004 Winter;10(4):317-36. doi: 10.1111/j.1527-3458.2004.tb00030.x. PMID: 15592581; PMCID: PMC6741761.[cited 2025 July 20]

10. Saadabadi A, Aripiprazole published in Stat Peals May 16, 2023[cited 2025 July 20]

11. Pondé MP, Freire AC. Increased Anxiety, Akathisia, and Suicidal Thoughts in Patients with Mood Disorder on Aripiprazole and Lamotrigine. Case Rep Psychiatry. 2015;2015:419746. doi: 10.1155/2015/419746. Epub 2015 Oct 5. PMID: 26509095; PMCID: PMC4609809.[cited 2025 July 20]

12. Tuplin EW, Holahan MR. Aripiprazole, A Drug that Displays Partial Agonism and Functional Selectivity. Curr Neuropharmacol. 2017 Nov 14;15(8):1192-1207. doi: 10.2174/1570159X15666170413115754. PMID: 28412910; PMCID: PMC5725548.[cited 2025 July 20]

Originally Published July 25, 2025 by Diane Ridaeus

This content has been reviewed and approved by:

ATMC Clinical Review Team

The ATMC Clinical Review Team includes licensed physicians and experienced healthcare professionals dedicated to ensuring the accuracy, quality, and integrity of our medical content. The team reviews articles for clinical accuracy, evidence-based guidance, and relevance while supporting Alternative to Meds Center’s whole-person approach to mental health, recovery, and long-term wellness.

Diane Ridaeus

Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.