Antipsychotic Medication – Vista Hill Center for Child and Youth Psychiatry https://www.vistahillccyp.org Providing ready access to board-certified child and adolescent psychiatrists who complete timely psychiatric evaluations and, as clinically indicated, provide follow-up care, including prescriptions to medications that support the social and emotional health of our clients. Mon, 14 Apr 2025 21:11:58 +0000 en-US hourly 1 https://wordpress.org/?v=7.0.2 https://www.vistahillccyp.org/wp-content/uploads/2016/12/cropped-vh_site_icon_512x512-32x32.png Antipsychotic Medication – Vista Hill Center for Child and Youth Psychiatry https://www.vistahillccyp.org 32 32 Psychotropic Drug-Related Weight Gain 4/16/25 https://www.vistahillccyp.org/3467-2/ https://www.vistahillccyp.org/3467-2/#comments Mon, 14 Apr 2025 21:11:58 +0000 https://www.smartcarebhcs.org/?p=3467 Weight gain is a common and often concerning side effect of psychotropic medications, including antidepressants, antipsychotics, lithium, and anticonvulsants. A systematic review by Sepulvida-Lizcano et al. found that 89% of frequently prescribed psychotropic medications are associated with metabolic alterations. This is particularly concerning for children and adolescents, who are at heightened risk of weight gain due to these drugs.

Psychotropic drug-related weight gain can lead to non-initiation, discontinuation, or dissatisfaction with treatment. Moreover, it contributes to obesity, which is linked to an increased risk of sleep apnea, type 2 diabetes, dyslipidemia, nonalcoholic fatty liver disease, and cardiovascular disease. Therefore, healthcare providers must be aware of the differential risks associated with psychotropic medications in order to evaluate these risks against the potential therapeutic benefits.

ANTIDEPRESSANTS

The risk of weight gain varies significantly across different antidepressants. Those associated with a high risk of weight gain include:

  • Amitriptyline
  • Citalopram
  • Clomipramine
  • Fluvoxamine
  • Mirtazapine
  • Nortriptyline
  • Paroxetine
  • Phenelzine

Moderate-risk antidepressants include:

  • Desipramine
  • Duloxetine
  • Escitalopram
  • Sertraline
  • Venlafaxine

Low-risk antidepressants include:

  • Agomelatine
  • Desvenlafaxine
  • Gepirone
  • Levomilnacipran
  • Moclobemide
  • Selegiline
  • Tranylcypromine
  • Vilazodone
  • Vortioxetine

Antidepressants with a neutral or weight-loss effect include:

  • Bupropion
  • Dextromethorphan-bupropion
  • Esketamine
  • Fluoxetine
  • Zuranolone

Antidepressants are thought to stimulate appetite and caloric intake due to their effects on cholinergic, histaminergic (H1), and serotonergic receptors.

          ANTIPSYCHOTICS

Antipsychotics, particularly second-generation antipsychotics, are strongly associated with weight gain. The medications most likely to cause significant weight gain include:

  • Clozapine
  • Olanzapine

Moderate-risk antipsychotics include:

  • Chlorpromazine
  • Olanzapine/samidorphan
  • Paliperidone
  • Quetiapine
  • Risperidone

Low-risk antipsychotics include:

  • Amisulpride
  • Aripiprazole
  • Asenapine
  • Brexpiprazole
  • Cariprazine
  • Haloperidol
  • Iloperidone
  • Ziprasidone

Antipsychotics with a neutral risk for weight gain include:

  • Lumateperone
  • Lurasidone

Risk factors for weight gain with antipsychotics include younger age, early stages of illness, antipsychotic-naïve status, lower pretreatment weight, and weight gain soon after starting treatment. Weight gain is dose-dependent with certain antipsychotics, such as olanzapine, and tends to increase with longer exposure. It is thought to result from a combination of factors, including high affinity and antagonism at histamine (H1), alpha-1 adrenergic, and 5-HT2C receptors; the absence of specific genetic variants (i.e., 5-HT2C receptor variant); and interactions between central dopamine and insulin signaling.

Lithium and Anticonvulsants. Among anticonvulsants, valproic acid carries the highest risk for weight gain. Lithium can also lead to weight gain, though the risk is generally considered lower than thought previously. Anticonvulsants with a low risk of weight gain include carbamazepine, gabapentin, oxcarbazepine, and pregabalin, while lamotrigine and topiramate have the lowest risk.

Preventing and managing psychotropic drug-related weight gain involves several strategies. These include encouraging lifestyle and behavioral modifications, prioritizing medications with a lower risk of weight gain, and adhering to metabolic monitoring guidelines. Additionally, providers can consider medications to promote weight gain.

For both adults and youth, metformin can be prescribed to prevent or treat weight gain related to antipsychotics. There is also some preliminary evidence suggesting that glucagon-like peptide-1 (GLP-1) agonists may help manage psychotropic-drug related weight gain, perhaps even more effectively than metformin; however, further research is needed.

References

Mansuri Z, Makani R, Trivedi C, et a. The role of metformin in treatment of weight gain associated with atypical antipsychotic treatment in children and adolescents: A systematic review and meta-analysis of randomized controlled trials. Frontiers in Psychiatry. 2022;13. doi:10.3389/fpsyt.2022.933570

McIntyre RS, Kwan ATH, Rosenblat JD, Teopiz KM, Mansur RB. Psychotropic Drug–Related Weight Gain and Its Treatment. American Journal of Psychiatry. 2024;181(1):26-38. doi:10.1176/appi.ajp.20230922

Sepúlveda-Lizcano L, Arenas-Villamizar VV, Jaimes-Duarte EB, et al. Metabolic Adverse Effects of Psychotropic Drug Therapy: A Systematic Review. European journal of investigation in health, psychology and education. 2023;13(8):1505-1520. doi:10.3390/ejihpe13080110

AUTHOR:

Dr. Kristen Kim, MD

Child, Adolescent and Adult Psychiatrist

Vista Hill Foundation

]]> https://www.vistahillccyp.org/3467-2/feed/ 2 Tapering Antipsychotic Medications in Children and Adolescents: Part 1 3/21/24 https://www.vistahillccyp.org/tapering-antipsychotic-medications-in-children-and-adolescents-3-21-24/ Wed, 20 Mar 2024 16:09:52 +0000 https://www.smartcarebhcs.org/?p=3288 Although pediatricians do not often initiate prescriptions for antipsychotic agents, this and a subsequent e-newsletter edition discuss important issues in their use that can be of relevance to pediatric practice, both in managing acute clinical situations and in managing care for youth with longer term needs for these medicines.
About 1% of children ages 7-12 and about 1.5% of adolescents ages 13-18 are prescribed antipsychotic medications1 some of which are FDA approved for minors with psychiatric diagnoses including schizophrenia, bipolar disorder (BD), and irritability in autism2.  This said, about 65% of antipsychotic medication prescribing is used off-label for issues such as severe aggression, agitation, disruptive behavior, irritability, and therapeutic augmentation when treating complex ADHD.  In these cases, antipsychotic medications may be of benefit but, in general, they should not be intended for high-dose or open-ended long-term use. This said, clinicians rarely consider or discuss discontinuation of antipsychotics or any psychotropic medications with their patients4. In this article and a subsequent article, we will discuss guidelines on when, how and how long to use antipsychotic medications and how to reduce or discontinue them in a safe and clinically appropriate manner.
Do antipsychotics work?
The short answer is yes, which is why they are used, both for FDA approved conditions and also for non-psychotic disorders that present with very challenging behaviors and/or crisis situations.   In high-risk scenarios, antipsychotics can be crucial for short-term to medium-term stabilization, such as keeping a child out of the psychiatric hospital, allowing a student to stay in a less restrictive school environment, and in reducing the risk of aggression or injury.  This said, research does not clearly show that antipsychotic medication is always meaningfully helpful in some of the situations where it is commonly prescribed, such as for severe ADHD or Oppositional Defiant Disorder5.
How long should a patient stay on an antipsychotic medication?
Antipsychotic medication use has primarily been studied and FDA approved for short-term use (up to 6 months) in children5or6 and, as yet, there are very few studies that assess benefits and side effects of longer-term antipsychotic use in children who are not suffering from a confirmed psychotic or bipolar disorder6or7.
Regardless of diagnosis, common safety issues and concerns related to antipsychotic medications include: metabolic effects like weight gain, diabetes and hyperlipidemia; somnolence; prolonged QTc interval; prolactin elevation; extrapyramidal symptoms; and neuroleptic malignant syndrome. For these reasons and others, one should always have a careful conversation with patients and their families when initiating a trial of an antipsychotic medication about the planned duration of treatment of the medication, which should include factors like severity of symptoms, the natural course of the condition being treated, the age of the child, and response to other psychosocial interventions.
Particularly when used for non-psychotic illnesses, careful determination on an individual case by case basis is important, keeping in mind that the duration of treatment and dosage considerations should be carefully reviewed and reconsidered over time. Even for clinical situations when there is FDA approval, as is the case for irritability in autism, one should carefully consider if the patient truly meets criteria for prescribing (e.g., in autism, such criteria would be serious aggression, self-injury, and/or severe mood lability) and if there could be another approach such as addressing sensory or communication difficulties or using of an alternative medication with a safer side effect profile.
Need Consultation or Information about Anti-psychotic medication?  
SmartCare’s On-Demand telephone consultation service is a readily accessible resource for primary care pediatricians needing support in managing patients with behavioral health challenges.  Call us at (858 880-6405).
Part 2 of today’s newsletter article will discuss clinical considerations in managing patients being treated with antipsychotic medications with a focus on pragmatic strategies in tapering and discontinuing these medications when indicated.
Author:

Charmi Patel Rao, MD

Associate Medical Director, Vista Hill Foundation

Health Science Assistant Clinical Professor for UCSD Department of Psychiatry

President, San Diego Academy of Child and Adolescent Psychiatry

References:
1 Olfson M et al., JAMA Psychiatry; 2015; 72(9):867-874.
2 Harrison J et al., Journal of Pediatric Health Care; 2012; 26(2): 139-145
3 Sohn M et al., Medicine 2016; 95(23): e3784
4 Dinnessen M et al., European Child and Adolescent Psychiatry; 2020; 29 (12): 1717-1727
5 Lentini G et al., Biomedicines 2022;10(11): 2818
6 Aman M et al., Journal of Child and Adolescent Psychopharmacology; 2015; 25(6):482-493
7  Singappuli P et al., CNS Spectrums 2022; 27(5):570-587
]]> Rationale for Considering Long-Acting Injectable Antipsychotic Medication 10/19/2017 https://www.vistahillccyp.org/rationale-for-considering-long-acting-injectable-antipsychotic-medication-10-19-2017/ Thu, 22 Feb 2018 19:14:25 +0000 http://www.smartcarebhcs.org/?p=2316 While schizophrenia is not a common diagnosis treated in the primary care setting, it does come up on occasion, especially when a patient is past the acute phase and in a more “stable” phase of his illness. Medication noncompliance goes hand in hand with the more severe psychiatric disorders, like schizophrenia and bipolar disorder. Really, treatment noncompliance is common in most chronic medical illnesses, like diabetes and hypertension, especially after a few years of treatment. This is why providers treating these disorders should consider long-acting injectable (LAI) medications in this population. It is also important for primary care providers to have some knowledge about LAI, because a patient with a history of schizophrenia who is not compliant with his mental health treatment might still be seeing his primary care provider for other medical concerns.

Studies have shown that in patients with schizophrenia, medication non-adherence (defined as taking the medication less than 80% of the prescribed time) reaches 75% after 2 years of taking a medication. The time course of schizophrenia, specifically time to remission after subsequent relapses, supports the use of LAI. In schizophrenia, it takes longer to achieve remission for each subsequent relapse into a psychotic episode. This statistic makes it that much more important to try to prevent future relapses in patients with schizophrenia.

There are several reasons why LAI are not considered more frequently. Most providers, including psychiatrists, rarely recommend it as a treatment after the first psychotic episode, and only half of psychiatrists recommend it after several episodes. Patients have concerns related to pain at the injection site, possible side effects, and burden of having to come into the medical office to receive their medication. Providers also have concerns related to insurance coverage and staffing issues.

LAI medications have been shown to be superior to oral antipsychotic medications in preventing psychiatric hospitalizations, taking medication non-adherence into consideration. The rates of longer term side effects, including metabolic effects and longer term extrapyramidal symptoms) are the same between oral antipsychotics and LAI, there is a lower risk of acute side effects, like sedation, orthostasis, and acute dystonia, with LAI compared to oral antipsychotics.

The first-generation antipsychotics available in injectable form include haloperidol (Haldol) and fluphenazine (Fluphenazine). The second-generation antipsychotics currently available in injectable form are risperidone (Risperdal Consta), paliperidone (Invega Sustenna: available in 1-month and 3-month formulations), olanzapine (Zyprexa Relprevv), aripriprazole (Abilify Maintena). It is important that patients are on the respective oral version of the medication in the initial stage while the LAI is loading into the system.

This information helps to support the argument to consider using LAI not just in stable patients with schizophrenia, but also in patients still in the acute phase. Here are some tips for talking with patients about the option of LAI. It is important to not say anything about compliance and adherence, to avoid the patient perceiving judgment. Instead one could ask “Would it be easier for you to take medication once a day or once a month?” and then following up with something like “We have the medication you are taking in a monthly version. Unfortunately it is not available in a pill, only an injection (avoid the word shot too!). Is that okay with you?”

In summary, medication non-adherence is the greatest single factor contributing to relapse risk in schizophrenia. Poor adherence starts at the onset of schizophrenia and is the norm, leading to functional decline. Patients should hear about depot options as early as possible and be educated about their benefits, including in their primary care setting.

 

 

 

 

 

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