Molindone

Mechanism-of-action classes: Adrenergic alpha-Antagonists; Dopamine Antagonists.

• Molindone Hydrochloride Tablets, USP are indicated for the management of schizophrenia. The efficacy of Molindone Hydrochloride Tablets, USP in schizophrenia was established in clinical studies which enrolled newly hospitalized and chronically hospitalized, acutely ill, schizophrenic patients as subjects.ICD-10: F20.9

• Molindone Hydrochloride Tablets are contraindicated in severe central nervous system depression (alcohol, barbiturates, narcotics, etc.) or comatose states, and in patients with known hypersensitivity to the drug.contraindicated

Initial and maintenance doses of Molindone Hydrochloride Tablets should be individualized. Initial Dosage Schedule The usual starting dosage is 50 to 75 mg/day. —Increase to 100 mg/day in 3 or 4 days. —Based on severity of symptomatology, dosage may be titrated up or down depending on individual patient response. —An increase to 225 mg/day may be required in patients with severe symptomatology. Elderly and debilitated patients should be started on lower dosage. Maintenance Dosage Schedule 1. Mild-5 mg to 15 mg three or four times a day. 2. Moderate-10 mg to 25 mg three or four times a day. Severe-225 mg/day may be required.

Increased Mortality in Elderly Patients with Dementia-Related Psychosis — Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Molindone Hydrochloride Tablets are not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING ). Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process.

CNS Effects The most frequently occurring effect is initial drowsiness that generally subsides with continued usage of the drug or lowering of the dose. Noted less frequently were depression, hyperactivity and euphoria. Neurological Extrapyramidal Symptoms Extrapyramidal symptoms noted below may occur in susceptible individuals and are usually reversible with appropriate management. Akathisia Motor restlessness may occur early. Parkinson Syndrome Akinesia, characterized by rigidity, immobility and reduction of voluntary movements and tremor, have been observed. Occurrence is less frequent than akathisia. Dystonia Class effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups. Tardive Dyskinesia Antipsychotic drugs are known to cause a syndrome of dyskinetic movements commonly referred to as tardive dyskinesia. The movements may appear during treatment or upon withdrawal of treatment and may be either reversible or irreversible (i.e., persistent) upon cessation of further antipsychotic administration.

Pregnancy Studies in pregnant patients have not been carried out. Reproduction studies have been performed in the following animals: Pregnant Rats oral dose— no adverse effect 20 mg/kg/day - 10 days no adverse effect 40 mg/kg/day - 10 days Pregnant Mice oral dose— slight increase resorptions 20 mg/kg/day - 10 days slight increase resorptions 40 mg/kg/day - 10 days Pregnant Rabbits oral dose— no adverse effect 5 mg/kg/day - 12 days no adverse effect 10 mg/kg/day - 12 days no adverse effect 20 mg/kg/day - 12 days Animal reproductive studies have not demonstrated a teratogenic potential. The anticipated benefits must be weighed against the unknown risks to the fetus if used in pregnant patients. Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Molindone Hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Symptomatic, supportive therapy should be the rule. Gastric lavage is indicated for the reduction of absorption of Molindone Hydrochloride which is freely soluble in water. Since the adsorption of Molindone Hydrochloride by activated charcoal has not been determined, the use of this antidote must be considered of theoretical value. Emesis in a comatose patient is contraindicated. Additionally, while the emetic effect of apomorphine is blocked by Molindone Hydrochloride in animals, this blocking effect has not been determined in humans. A significant increase in the rate of removal of unmetabolized Molindone Hydrochloride from the body by forced diuresis, peritoneal or renal dialysis would not be expected. (Only 2% of a single ingested dose of Molindone Hydrochloride is excreted unmetabolized in the urine). However, poor response of the patient may justify use of these procedures. While the use of laxatives or enemas might be based on general principles, the amount of unmetabolized Molindone Hydrochloride in feces is less than 1%.

• Mar 20, 2015ANDAANDA090453Epic Pharma Llc

1. 1Hypersensitivity150%
2. 2Nephropathy Toxic150%

Recent PubMed references pinned to Molindone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Time to Clinical Response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study.
  Journal of child and adolescent psychopharmacology · 2021 · Taylor JH, Appel S, Eli M, et al.
  PMID 32633541DOI 10.1089/cap.2020.0030
• Mimicking of Phase I Metabolism Reactions of Molindone by HLM and Photocatalytic Methods with the Use of UHPLC-MS/MS.
  Molecules (Basel, Switzerland) · 2020 · Gawlik M, Savic V, Jovanovic M, et al.
  PMID 32192164DOI 10.3390/molecules25061367
• Comments on "Reproductive toxicology studies supporting the safety of molindone, a dopamine receptor antagonist" (Gopalakrishnan et al., Birth Defects Research. 2018; 110(16):1250-1262).
  Birth defects research · 2019 · Wise LD
  PMID 30729747DOI 10.1002/bdr2.1471
• Response to comments on "Reproductive toxicology studies supporting the safety of molindone, a dopamine receptor antagonist".
  Birth defects research · 2019 · Gopalakrishnan G, Ganiger S, White TEK, et al.
  PMID 30632696DOI 10.1002/bdr2.1447
• Reproductive toxicology studies supporting the safety of molindone, a dopamine receptor antagonist.
  Birth defects research · 2018 · Gopalakrishnan G, Ganiger S, White TEK, et al.
  PMID 30230712DOI 10.1002/bdr2.1381
• Toxicity assessment of molindone hydrochloride, a dopamine D2/D5 receptor antagonist in juvenile and adult rats.
  Toxicology mechanisms and methods · 2017 · Krishna G, Gopalakrishnan G, Goel S, et al.
  PMID 28142338DOI 10.1080/15376516.2017.1288768
• In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist molindone hydrochloride.
  Environmental and molecular mutagenesis · 2016 · Krishna G, Gopalakrishnan G, Goel S, et al.
  PMID 27040600DOI 10.1002/em.22007
• Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice.
  Reproductive toxicology (Elmsford, N.Y.) · 2015 · Krishna G, Ganiger S, Kannan K, et al.
  PMID 26327279DOI 10.1016/j.reprotox.2015.08.006

The 8 most recently updated of 8 ClinicalTrials.gov registrations naming Molindone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Phase 2a Study of Safety and Tolerability of SPN-810 in Children With ADHD and Persistent Serious Conduct Problems
  Completed · Phase 2 · Interventional · 78 enrolled · Supernus Pharmaceuticals, Inc.
  NCT00626236updated 2025-12-09
• A Study to Assess Stroke Risk Among Users of Typical Versus Atypical Antipsychotics Stratified by Broad Age Group
  Completed · Observational · 1,234,412 enrolled · Janssen Research & Development, LLC
  NCT04002700updated 2025-06-25
• Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 4)
  Terminated · Phase 3 · Interventional · 491 enrolled · Supernus Pharmaceuticals, Inc.
  NCT02691182updated 2024-05-16
• Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 2)
  Completed · Phase 3 · Interventional · 297 enrolled · Supernus Pharmaceuticals, Inc.
  NCT02618434updated 2024-03-18
• Treatment of Impulsive Aggression in Subjects With ADHD in Conjunction With Standard ADHD Treatment (CHIME 1)
  Completed · Phase 3 · Interventional · 333 enrolled · Supernus Pharmaceuticals, Inc.
  NCT02618408updated 2024-01-02
• Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care
  Completed · Observational · 3,520 enrolled · Daniel Benjamin
  NCT01431326updated 2023-09-06
• Open-Label, Extension Study to 810P202
  Completed · Phase 2 · Interventional · 78 enrolled · Supernus Pharmaceuticals, Inc.
  NCT01416064updated 2017-05-02
• Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
  Completed · Phase 4 · Interventional · 116 enrolled · University of North Carolina, Chapel Hill
  NCT00053703updated 2014-03-26

Frequently asked questions

How does Molindone work?

Mechanism-of-action classes: Adrenergic alpha-Antagonists; Dopamine Antagonists.

What is Molindone used for?

According to FDA labeling, Molindone carries indications including: Molindone Hydrochloride Tablets, USP are indicated for the management of schizophrenia. The efficacy of Molindone Hydrochloride Tablets, USP in schizophrenia was established in clinical studies which enrolled newly hospitalized and chronically hospitalized, acutely ill, schizophrenic patients as subjects.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Molindone?

Molindone is classified as Indole derivatives, Typical Antipsychotic, Adrenergic alpha-Antagonists, Dopamine Antagonists, Decreased Central Nervous System Organized Electrical Activity, Decreased Dopamine Activity, Hypothalamic Endocrine Activity Alteration.

What are the contraindications for Molindone?

Molindone labeling lists contraindications including: Molindone Hydrochloride Tablets are contraindicated in severe central nervous system depression (alcohol, barbiturates, narcotics, etc.) or comatose states, and in patients with known hypersensitivity to the drug.. Always consult the full prescribing information and a clinician.