Antipsychotic drugs side effects and danger, natural and alternative ways to decrease antipsychotic medication risks
May 16 2017 by
Ray Sahelian, M.D.

Schizophrenia is a chronic disorder usually necessitating lifelong treatment. Although atypical antipsychotic agents have improved outcomes in schizophrenia, their clinical potential remains limited by patients poor adherence to medication. Long-acting antipsychotics were developed in the 1960s to enhance treatment adherence and simplify the medication process.
   There are many antipsychotic drugs that have helped patients with schizophrenia. However, which antipsychotic medication is best? It was reported that Pharmaceutical giant Eli Lilly and Co. funded five studies that compared its antipsychotic drug Zyprexa with Risperdal, a competing drug made by Janssen. All five showed Zyprexa was superior in treating schizophrenia. But when Janssen sponsored its own studies comparing the two antipsychotic drugs, Risperdal came out ahead in two out of three. In fact, when a psychiatrist John Davis, analyzed every publicly available trial funded by the pharmaceutical industry pitting six new antipsychotic drugs against one another, nine in 10 showed that the best drug was the one made by the company funding the study.


Natural therapy for those on antipsychotic drugs
BMC Complement Alternative Medicine. 2012. Antipsychotic-like activity of noni (Morinda citrifolia) in mice. The present study results demonstrated the antidopaminergic effect of Morinda citrifolia in mice, suggesting that noni has antipsychotic-like activity which can be utilized in the treatment of psychiatric disorders.


Quercetin and other flavonoids and polyphenols may be helpful in reversing some antipsychotic drug side effects.


Quercetin, a bioflavonoid, reverses haloperidol-induced catalepsy.
Methods Find Exp Clin Pharmacol. 2004.
Neuroleptics are extensively used in the treatment of schizophrenia and other affective disorders. Unfortunately their use is often associated with distressing side effects involving the extrapyramidal tract, such as Parkinsonism and tardive dyskinesia. Neuroleptic-induced catalepsy has long been used as a model for extrapyramidal side effects such as Parkinsonian-like bradykinesia associated with antipsychotic use in humans. In the present study, haloperidol was administered to mice to induce catalepsy. Pretreatment with quercetin dose-dependently reduced the catalepsy score in haloperidol-treated animals. The findings of the present study strongly suggest that quercetin can be screened as a potential drug candidate or as an adjuvant for the treatment of neuroleptic-induced extrapyramidal side effects.


Inhibitory effects of polyphenol compounds on lipid peroxidation caused by antipsychotics (haloperidol and amisulpride) in human plasma in vitro.
World J Biol Psychiatry. 2009. Department of Affective and Psychotic Disorders, Medical University of Lodz, Czechoslowacka, Lodz, Poland.
Plant antioxidants protect cells against oxidative stress. Since oxidative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics, the aim of the study was to assess whether there is a difference between a first-generation antipsychotic haloperidol and a second-generation antipsychotic amisulpride action on peroxidation of plasma lipids, and to establish the effects of polyphenol compounds resveratrol and quercetin and the antipsychotics action on this process in vitro. Our results show that haloperidol, contrary to amisulpride caused a distinct increase of lipid peroxidation. Polyphenols reduced significantly lipid peroxidation caused by haloperidol.


Q. Can a person take saw palmetto or pygeum if using an antipsychotic medication, an atypical antipsychotic?
   A. Probably, as long as the dosages are low.

Q. Does choline interfere with antipsychotic medication?
   A. Perhaps since choline increases levels of acetycholine.

Q. Is there such thing as a natural antipsychotic? I'm on haldol and am interested in investigating an alternative.
   A. We are not aware at this time of a natural antipsychotic, although it is an interesting idea to research whether fish oils can help stabilize symptoms to a slight degree. This is just a guess at this time.


Q. My son of 32 yrs old with bipolar disorder is currently taking Prolyxin shot, Depakote, Xyprexa, Antabuse and Benadryl. Is it safe for him i.e. no side effects, if he takes 5-Htp, Mind Power Rx? He also needs something to increase his physical energy as he gets easily tired and takes naps. Please suggest something of this problem.
   A. It is very difficult to predict the interactions between medications and natural supplements, let alone when there are multiple potent medications that are involved. Research in these areas is very limited. His physician needs to make the final decision.


Are the newer drugs better?
Schizophrenia is a severe psychiatric disorder in which patients experience distorted thinking, hallucinations and abnormal emotions. The disease is classified as a psychotic disorder, meaning that patients are often not completely in touch with reality. Therefore, the disease is treated with antipsychotic drugs, including the newer, "atypical" antipsychotic drugs clozapine and olanzapine as well as the older antipsychotic drug haloperidol.


Many people taking powerful psychiatric medications that increase their risk of weight gain and diabetes are prescribed those drugs when there's little evidence that they will get any benefit from them. According to G. Caleb Alexander, MD, an assistant professor in the department of medicine at the University of Chicago Hospitals, even when these atypical antipsychotics are prescribed as recommended, they may not be safer or more effective than the less expensive, older medications that they've apparently replaced.


Dosage and frequency of medications
The widely held view that maintenance treatment of stabilized patients with schizophrenia must be administered every day is refuted by a Canadian study. The researchers found that patients taking antipsychotic meds every other day were no more likely to relapse than those on a daily dosing schedule. J Clin Psychiatry 2010.


Schizophrenia medication
Typical and atypical antipsychotic agents differ in their receptor-binding affinities, which are related to their differing side-effect profiles. Novel therapeutic strategies include normalisation of synaptic dopamine or serotonin levels, serotonin receptor antagonism and modulation of cerebral protein synthesis.
    A head-to-head comparison of five schizophrenia drugs found that most newer treatments are no better than an older generic drug, despite their higher cost. The lone exception, Eli Lilly and Co.'s Zyprexa, may be better than the other medicines but users experienced dramatic weight gain and developed a higher risk of diabetes. The drug is also the most expensive. The study used the amount of time patients stayed on a drug to help gauge its effectiveness. In all, 74 percent of the 1,432 volunteers at 57 study sites stopped taking the medication they were originally assigned. Only the schizophrenics taking Zyprexa, also known as olanzapine, stuck with it significantly longer than the other four. But even 64 percent stopped taking it after 18 months. The discontinuation rate was higher among the other four drugs: Seroquel (quetiapine) from AstraZeneca Plc; Risperdal (risperidone) from Janssen Pharmaceutical, a wholly owned unit of Johnson & Johnson; Geodon (ziprasidone) from Pfizer Inc., and perphenazine, which has been around since the 1950s and is available in generic form. One surprise was that perphenazine's side effects such as tremor, rigidity, stiff movements and muscle restlessness were not as common as expected. Patients tolerated it just as well as some of the newer drugs, and it was no less effective. And it was far cheaper. At the average doses used in the study, a month's supply of perphenazine capsules costs about $50 - compared with roughly $390 for Geodon, $425 for Risperdal, $475 for Seroquel, and $660 for Zyprexa.

     Atypical antipsychotics exhibit a reduced risk for tardive dyskinesia compared with conventional drugs. However, weight gain is more common with some atypical drugs (especially clozapine and olanzapine). Both conventional and atypical antipsychotics have been associated with diabetes, with most reports implicating both clozapine and olanzapine. Atypical antipsychotics (unlike conventional drugs) have little or no effect on QT and are not associated with sudden death.


Long term use of antipsychotic medications has a negative impact on brain structure.


Blood sugar and diabetes
Antipsychotic meds may raise blood sugar. High levels of sugar in the blood, also known as hyperglycemia, is a common finding in individuals taking atypical antipsychotics who originally had normal blood sugar levels.


Alzheimer's disease no benefit
Any possible benefits atypical antipsychotics may offer against psychosis, aggression, or agitation in patients with Alzheimer's disease are offset by the occurrence of side effects. Although atypical antipsychotics are widely used in patients with Alzheimer's disease, there is limited data regarding their safety and efficacy for this indication.
"Alzheimer’s Drugs Offer No Help, Study Finds" was an article in the October 12 issue of New York Times written by Benedict Carey. According to this interesting article, the medicines most commonly prescribed for agitation and delusions in Alzheimer’s disease are no more effective than placebos, and put them at risk of serious side effects, including confusion, sleepiness and Parkinson’s disease-like symptoms. The drugs tested in the study — Zyprexa from Eli Lilly; Seroquel from AstraZeneca; and Risperdal from Janssen Pharmaceutical — belong to a class of medications known as atypical antipsychotics. These antipsychotic drugs are used to treat schizophrenia and other psychoses, and are commonly prescribed for elderly patients in long-term care facilities. About a third of the estimated 2.5 million Medicare beneficiaries in nursing homes in the United States have taken the medications.
   Antipsychotic medication to manage dementia-related behavioral or psychological symptoms is associated with increased risk of death. Elderly patients with Alzheimer's disease who are treated with second-generation antipsychotics gain weight and have lipid abnormalities which could increase the risk for heart disease. American Journal of Psychiatry, April 17, 2009.


Antipsychotic drugs not helpful for aggression
Haloperidol and risperidone, long used to treat aggressive behavior in people with limited intelligence, do not work and should not be prescribed for these patients. For the past several decades doctors have treated aggression in people who are not psychotic with these drugs, but placebos seem to do a better job.


Bone Fractures
Both conventional and atypical antipsychotics increase the risk of femoral fracture in institutionalized elderly most likely due to gait and movement disorders which increase the risk of falling.


Heart disease
Patients with severe mental illness live an average of 16 years less than people in the general population. Heart disease, not suicide, is the major cause of death in these patients and antipsychotic drugs are a factor. There is increased risk of heart attack in older patients who take these medications.


Metabolic syndrome, elevated blood sugar, diabetes

Treatment with clozapine, considered one of the most effective antipsychotic medication, appears to increase the risk of developing metabolic syndrome x. Metabolic syndrome is a cluster of conditions that includes obesity, high triglyceride levels, high blood pressure and high blood sugar levels. People with the syndrome are at increased risk for heart attacks and stroke. The findings stem from a study of 93 outpatients who were receiving clozapine as a treatment for schizophrenia or schizoaffective disorder. The rate of metabolic syndrome in this group was compared with that seen in 2701 control subjects matched by age, body weight for height, and race or ethnicity. Nearly 54 percent of clozapine -treated patients had metabolic syndrome compared with 20 percent of subjects in the comparison group. In addition to clozapine use, other risk factors for metabolic syndrome included older age and being overweight. American Journal of Psychiatry, July 2006.


Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different.


Mortality increased, use in elderly
Commonly prescribed doses of haloperidol, olanzapine, and risperidone are associated with an increase in mortality in elderly patients with dementia.
Antipsychotics such as haloperidol and risperidone are associated with a significant and dose-related increase in mortality in elderly patients with dementia, compared with antidepressants or nonuse.

Antipsychotics can be safely withdrawn from many dementia patients in long-term care facilities. The drugs can be withdrawn and supplanted with behavior-centered care.


Weight gain
Up to 80 percent of patients taking antipsychotic drugs to treat schizophrenia and other mental conditions gain a significant amount of weight. To assess if drug-related weight gain can be attenuated, investigators used early behavioral intervention (EBI), designed to teach patients ways to maximize control over their weight, using nutrition, exercise and behavioral strategies. Dr. Mario Alvarez-Jimenez of the University Hospital Marques de Valdecilla in Santander, Spain, and others randomized 61 antipsychotic-naïve patients diagnosed with a psychiatric disorder to one of three treatments: risperidone (Risperdal), haloperidol (Haldol), or olanzapine (Zyprexa). Patients were then randomized to EBI or routine care. EBI was initiated at the same time as drug therapy, with the intention of preventing or minimizing weight gain. By the end of the study period, patients randomized to EBI gained a mean of 4.1 kg compared with a mean gain of 6.9 kg in the routine care patients, which was a significant difference. BMI -- the ratio of height to weight -- increased by 1.40 in the EBI group compared with 2.39 in patients who received routine, again a significant difference favoring EBI. A weight gain of more than 7 percent over baseline occurred in 39.3 percent of EBI patients compared with 78.8 percent in those receiving routine care. Journal of Clinical Psychiatry 2006.


The second generation antipsychotics clozapine and olanzapine frequently induce weight gain. Both clozapine and olanzapine can induce food craving and binge eating, however, olanzapine possibly to a greater extent.


Combination medication prescription
Schizophrenics who take two antipsychotic drugs show no more improvement than those on a single drug, raising doubts about the benefit of using multiple medicines to treat the disease. A study, published in the New England Journal of Medicine, tested 68 patients who responded poorly to clozapine, the generic version of Novartis AG's Clozaril. Half the group took clozapine along with Johnson & Johnson's antipsychotic Risperdal. The other half were given clozapine with a placebo. Both groups showed the same degree of improvement during the 26-week trial, but there was a slight deterioration in memory among the ones taking Risperdal. The results offer no support for the idea of prescribing multiple drugs, at least from the same class, especially to people who got little help from clozapine.


Personality Disorder Treatment
The anti-psychotic drug Abilify (aripiprazole) appears to be effective for patients with borderline personality disorder, often leading to improvements in health-related quality of life and interpersonal problems. Personality disorder is a type of mental illness in which people have trouble functioning with others. It can be associated with depression and psychopathological symptoms. A few antipsychotic agents have been used in therapy for patients with borderline personality disorder. The most common side effects reported with Abilify were headache, insomnia, nausea, numbness, constipation and anxiety. American Journal of Psychiatry, May 2006.


Asperger's disease
The results of a study published in the Journal of Clinical Psychiatry suggest that symptoms of Asperger's disorder are improved by treatment with the atypical antipsychotic drug risperidone. Asperger's disorder has been described as a high-functioning form of autism. While patients with the disease have higher intellectual capacity than those with autism, they have a lower social capacity. The researchers enrolled 13 male patients between the ages of 6 and 18 years from March 13, 2002 to August 11, 2003. All of the patients were started on a standard dose of risperidone, which was increased to produce the maximum benefit with tolerable side effects. After 12 weeks, treatment with risperidone was associated with significant improvements in disease symptoms, the authors note. In addition, the severity of depression, a common feature of the disease, also improved with the drug. Journal of Clinical Psychiatry, December 2005.


Tourettes syndrome
The most frequently used drugs for tics arising from Tourette's syndrome are antipsychotics (mainly pimozide and haloperidol) and clonidine.


Heat Intolerance

Because antipsychotic medications can impair the body's heat regulation, patients receiving these medications should be cautioned against overexertion during hot and humid weather, and should be advised to seek cool environments and drink adequate amounts of fluids. Development of hyperthermia in individuals taking antipsychotic medication is potentially life-threatening, and requires immediate intervention and supportive measures.


Are Children Being Given too many of these medicines?
Soaring numbers of American children are being prescribed anti-psychotic drugs — in many cases, for attention deficit disorder or other behavioral problems for which these medications have not been proven to work. The annual number of children prescribed anti-psychotic drugs jumped fivefold between 1995 and 2002, to an estimated 2.5 million. But more than half of the prescriptions were for attention deficit adhd and other non-psychotic conditions. The increasing use of anti-psychotics since the mid-1990s corresponds with the introduction of costly and heavily marketed medications such as Zyprexa and Risperdal. The packaging information for both says their safety and effectiveness in children have not been established. Anti-psychotics are intended for use against schizophrenia and other psychotic illnesses. The drugs, which typically cost several dollars per pill, are considered safer than older anti-psychotics — at least in adults — but they still can have serious side effects, including weight gain, elevated cholesterol and diabetes.
     The prescription of antipsychotic medications for children and adolescents in the U.S. increased nearly 6-fold between 1993 and 2002. FDA has approved only three antipsychotic drugs — haloperidol, thioridazine hydrochloride and pimozide — for use in patients younger than 18 years, but most of the prescriptions written are for newer medications. Approximately 90 percent of antipsychotics prescribed are for the second-generation drugs — clozapine, risperidone, olanzapine, and quetiapine. None of these drugs is approved for treating adolescents or children. These drugs were prescribed primarily for disruptive behavior disorders, mood disorders, or pervasive developmental disorders or mental retardation. Only 14 percent were prescribed for psychotic disorders. Not enough is known about the metabolic effects of newer antipsychotics, particularly the long-term effects in young people.