Bupropion inhibits the reuptake of noradrenaline and dopamine, making it an NDRI.

Mechanisms of Action of Different Drugs

Understanding the mechanisms of action of different drugs is crucial for medical professionals. It is a common topic in exams and can earn easy marks if studied well. This article provides a list of drugs and their mechanisms of action in different categories such as antidepressants, anti dementia drugs, mood stabilizers, anxiolytic/hypnotic drugs, antipsychotics, drugs of abuse, and other drugs. For example, mirtazapine is a noradrenaline and serotonin specific antidepressant that works as a 5HT2 antagonist, 5HT3 antagonist, H1 antagonist, alpha 1 and alpha 2 antagonist, and moderate muscarinic antagonist. Similarly, donepezil is a reversible acetylcholinesterase inhibitor used as an anti dementia drug, while valproate is a GABA agonist and NMDA antagonist used as a mood stabilizer. The article also explains the mechanisms of action of drugs such as ketamine, phencyclidine, buprenorphine, naloxone, atomoxetine, varenicline, disulfiram, acamprosate, and sildenafil.

Mechanisms of Action of Different Drugs

Understanding the mechanisms of action of different drugs is crucial for medical professionals. It is a common topic in exams and can earn easy marks if studied well. This article provides a list of drugs and their mechanisms of action in different categories such as antidepressants, anti dementia drugs, mood stabilizers, anxiolytic/hypnotic drugs, antipsychotics, drugs of abuse, and other drugs. For example, mirtazapine is a noradrenaline and serotonin specific antidepressant that works as a 5HT2 antagonist, 5HT3 antagonist, H1 antagonist, alpha 1 and alpha 2 antagonist, and moderate muscarinic antagonist. Similarly, donepezil is a reversible acetylcholinesterase inhibitor used as an anti dementia drug, while valproate is a GABA agonist and NMDA antagonist used as a mood stabilizer. The article also explains the mechanisms of action of drugs such as ketamine, phencyclidine, buprenorphine, naloxone, atomoxetine, varenicline, disulfiram, acamprosate, and sildenafil.

The effectiveness of minocycline, a tetracycline antibiotic, in providing neuroprotection has been observed in vitro. This study aimed to evaluate the impact of minocycline on negative symptoms in individuals diagnosed with schizophrenia at the beginning of the trial and after one year of follow-up. Minocycline is recognized for its ability to be well-tolerated in acne treatment and its capacity to cross the blood-brain barrier. Preliminary findings have indicated that it may be effective in preventing the onset of negative symptoms in schizophrenia. There have been no clinical trials conducted on the other antibiotics.

, coma, respiratory depression (rare)

Unlike other antidepressants, agomelatine (Valdoxan) does not affect serotonin transmission and is a melatonin agonist. It has a good safety profile and there have been no reported cases of hyponatraemia associated with its use. On the other hand, the other listed antidepressants have been linked to hyponatraemia.

Amantadine and QTc Prolongation

Amantadine is a medication used to treat Parkinson’s disease and influenza. It has been associated with QTc prolongation, which can increase the risk of Torsades de points. Therefore, caution should be exercised when prescribing amantadine to patients with risk factors for QT prolongation. If a patient is already taking amantadine and develops a prolonged QTc interval, the medication should be discontinued and an alternative treatment considered. It is important to monitor the QTc interval in patients taking amantadine, especially those with risk factors for QT prolongation.

Clozapine is an atypical antipsychotic drug that acts as an antagonist at various receptors, including dopamine, histamine, serotonin, adrenergic, and cholinergic receptors. It is mainly metabolized by CYP1A2, and its plasma levels can be affected by inducers and inhibitors of this enzyme. Clozapine is associated with several side effects, including drowsiness, constipation, weight gain, and hypersalivation. Hypersalivation is a paradoxical side effect, and its mechanism is not fully understood, but it may involve clozapine agonist activity at the muscarinic M4 receptor and antagonist activity at the alpha-2 adrenoceptor. Clozapine is also associated with several potentially dangerous adverse events, including agranulocytosis, myocarditis, seizures, severe orthostatic hypotension, increased mortality in elderly patients with dementia-related psychosis, colitis, pancreatitis, thrombocytopenia, thromboembolism, and insulin resistance and diabetes mellitus. The BNF advises caution in using clozapine in patients with prostatic hypertrophy, susceptibility to angle-closure glaucoma, and adults over 60 years. Valproate should be considered when using high doses of clozapine, plasma levels > 0.5 mg/l, of when the patient experiences seizures. Myocarditis is a rare but potentially fatal adverse event associated with clozapine use, and its diagnosis is based on biomarkers and clinical features. The mortality rate of clozapine-induced myocarditis is high, and subsequent use of clozapine in such cases leads to recurrence of myocarditis in most cases.

Immunologic Adverse Drug Reactions

Immunologic adverse drug reactions account for a small percentage of all adverse drug reactions, ranging from 5 to 10%. These reactions are classified using the Gell and Coombs system, which categorizes them into four groups: Type I, Type II, Type III, and Type IV reactions.

Type I reactions occur when a drug-IgE complex binds to mast cells, leading to the release of histamine and other inflammatory mediators. These reactions typically cause anaphylaxis, urticaria, and bronchospasm and occur within minutes to hours after exposure.

Type II reactions occur when an IgG of IgM antibody binds to a cell that has been altered by a drug-hapten. These reactions often manifest as blood abnormalities, such as thrombocytopenia and neutropenia, and their timing is variable.

Type III reactions occur when drug-antibody complexes activate the complement system, leading to fever, rash, urticaria, and vasculitis. These reactions occur 1 to 3 weeks after exposure.

Type IV reactions arise when the MHC system presents drug molecules to T cells, resulting in allergic contact dermatitis and rashes. These reactions occur 2 to 7 days after cutaneous exposure.

Unless there is a specific reason stated in the vignette, the first-line treatment for depression with medication is typically a selective serotonin reuptake inhibitor (SSRI). However, an alternative option may be duloxetine, which is a serotonin-norepinephrine reuptake inhibitor (SNRI).

SSRIs, of selective serotonin reuptake inhibitors, are the first-line treatment for depression in most patients. However, some SSRIs have different side effects and interactions than others. For example, fluoxetine, fluvoxamine, and paroxetine have a higher propensity for drug interactions, while citalopram is useful for elderly patients as it is associated with lower risks of drug interactions. SSRIs should be used with caution in children and adolescents, and fluoxetine is the drug of choice in this population.

Common side effects of SSRIs include gastrointestinal symptoms, sedation, and sexual dysfunction. Paroxetine is considered the most sedating and anticholinergic, while vortioxetine is associated with the least sexual dysfunction. Patients taking SSRIs are at an increased risk of gastrointestinal bleeding, and a proton pump inhibitor should be prescribed if they are also taking an NSAID.

When stopping a SSRI, the dose should be gradually reduced over a 4 week period, except for fluoxetine. Paroxetine has a higher incidence of discontinuation symptoms, which can include mood changes, restlessness, difficulty sleeping, and gastrointestinal symptoms.

SSRIs can also have interactions with other medications, such as NSAIDs, warfarin/heparin, aspirin, and triptans. Patients should be reviewed by a doctor after starting antidepressant therapy, and if they make a good response, they should continue treatment for at least 6 months after remission to reduce the risk of relapse.

In patients who have had a myocardial infarction, approximately 20% develop depression. SSRIs are the preferred antidepressant group post-MI, but they can increase the bleeding risk, especially in those using anticoagulation. Mirtazapine is an alternative option, but it too is associated with bleeding. The SADHART study found sertraline to be a safe treatment for depression post-myocardial infarction.

Serotonin Syndrome and Neuroleptic Malignant Syndrome are two conditions that can be difficult to differentiate. Serotonin Syndrome is caused by excess serotonergic activity in the CNS and is characterized by neuromuscular abnormalities, altered mental state, and autonomic dysfunction. On the other hand, Neuroleptic Malignant Syndrome is a rare acute disorder of thermoregulation and neuromotor control that is almost exclusively caused by antipsychotics. The symptoms of both syndromes can overlap, but there are some distinguishing clinical features. Hyper-reflexia, ocular clonus, and tremors are more prominent in Serotonin Syndrome, while Neuroleptic Malignant Syndrome is characterized by uniform ‘lead-pipe’ rigidity and hyporeflexia. Symptoms of Serotonin Syndrome usually resolve within a few days of stopping the medication, while Neuroleptic Malignant Syndrome can take up to 14 days to remit with appropriate treatment. The following table provides a useful guide to the main differentials of Serotonin Syndrome and Neuroleptic Malignant Syndrome.

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.

QTc Prolongation: Risks and Identification

The QT interval is a measure of the time it takes for the ventricles to repolarize and is calculated from the beginning of the QRS complex to the end of the T wave. However, the QT interval varies with the heart rate, making it difficult to use a single number as a cut-off for a prolonged QT. Instead, a corrected QT interval (QTc) is calculated for each heart rate using various formulas. A QTc over the 99th percentile is considered abnormally prolonged, with approximate values of 470 ms for males and 480 ms for females.

Prolonged QT intervals can lead to torsade de pointes (TdP), a polymorphic ventricular tachycardia that can be fatal if it degenerates into ventricular fibrillation. TdP is characterized by a twisting of the QRS complexes around an isoelectric line and is often asymptomatic but can also be associated with syncope and death. An accurate diagnosis requires an ECG to be recorded during the event. It is important to note that an increase in the QT interval due to a new conduction block should not be considered indicative of acquired LQTS and risk for TdP.

The First Pass Effect in Psychiatric Drugs

The first-pass effect is a process in drug metabolism that significantly reduces the concentration of a drug before it reaches the systemic circulation. This phenomenon is related to the liver and gut wall, which absorb and metabolize the drug before it can enter the bloodstream. Psychiatric drugs are not exempt from this effect, and some undergo a significant reduction in concentration before reaching their target site. Examples of psychiatric drugs that undergo a significant first-pass effect include imipramine, fluphenazine, morphine, diazepam, and buprenorphine. On the other hand, some drugs undergo little to no first-pass effect, such as lithium and pregabalin.

Orally administered drugs are the most affected by the first-pass effect. However, there are other routes of administration that can avoid of partly avoid this effect. These include sublingual, rectal (partly avoids first pass), intravenous, intramuscular, transdermal, and inhalation. Understanding the first-pass effect is crucial in drug development and administration, especially in psychiatric drugs, where the concentration of the drug can significantly affect its efficacy and safety.

Sedatives and Liver Disease

Sedatives are commonly used for their calming effects, but many of them are metabolized in the liver. Therefore, caution must be taken when administering sedatives to patients with liver disease. The Maudsley Guidelines recommend using low doses of the following sedatives in patients with hepatic impairment: lorazepam, oxazepam, temazepam, and zopiclone. It is important to note that zopiclone should also be used with caution and at low doses in this population. Proper management of sedative use in patients with liver disease can help prevent further damage to the liver and improve overall patient outcomes.

Understanding Biotransformation: A Metabolic Process for Excretion

Biotransformation is a metabolic process that occurs primarily in the liver, but also in other organs such as the kidneys, intestine, adipose, skin, and lungs. Its main function is to facilitate the excretion of both exogenous and endogenous substances by altering their chemical structures through a series of reactions. Enzymes found in the cytoplasm, endoplasmic reticulum, and mitochondria of cells catalyze these reactions, which can cause the substrate to become inactive, active, of even toxic.

Biotransformation is divided into three phases. Phase I reactions involve oxidation, reduction, of hydrolysis of the drug, yielding a polar, water-soluble metabolite that is often still active. Phase II reactions consist of adding hydrophilic groups to the original molecule, a toxic intermediate, of a nontoxic metabolite formed in phase I, to increase its polarity. The most common method is conjugation with glucuronic acid, but other groups such as sulphate, amino acids, acetate, and methyl can also be added. Phase III reactions occur post-phase II, where a chemical substance can undergo further metabolism and excretion through active transport into the urinary of hepatobiliary system.

Understanding biotransformation is crucial in pharmacology and toxicology, as it affects the efficacy and toxicity of drugs and other substances. By facilitating the excretion of these substances, biotransformation helps maintain homeostasis in the body and prevent accumulation of potentially harmful compounds.

Antidepressants with Active Metabolites

Many antidepressants have active metabolites that can affect the body’s response to the medication. For example, amitriptyline has nortriptyline as an active metabolite, while clomipramine has desmethyl-clomipramine. Other antidepressants with active metabolites include dosulepin, doxepin, imipramine, lofepramine, fluoxetine, mirtazapine, trazodone, and venlafaxine.

These active metabolites can have different effects on the body compared to the original medication. For example, nortriptyline is a more potent inhibitor of serotonin and norepinephrine reuptake than amitriptyline. Similarly, desipramine, the active metabolite of imipramine and lofepramine, has a longer half-life and is less sedating than the original medication.

It is important for healthcare providers to be aware of the active metabolites of antidepressants when prescribing medication and monitoring patients for side effects and efficacy.

A Historical Note on the Development of Zimelidine, the First Selective Serotonin Reuptake Inhibitor

In 1960s, evidence began to emerge suggesting a significant role of serotonin in depression. This led to the development of zimelidine, the first selective serotonin reuptake inhibitor (SSRI). Zimelidine was derived from pheniramine and was marketed in Europe in 1982. However, it was removed from the market in 1983 due to severe side effects such as hypersensitivity reactions and Guillain-Barre syndrome.

Despite its short-lived availability, zimelidine paved the way for the development of other SSRIs such as fluoxetine, which was approved by the FDA in 1987 and launched in the US market in 1988 under the trade name Prozac. The development of SSRIs revolutionized the treatment of depression and other mood disorders, providing a safer and more effective alternative to earlier antidepressants such as the tricyclics and MAO inhibitors.

– Lithium toxicity occurs at levels above 1.4 mmol/L
– Symptoms include anorexia, diarrhea, vomiting, ataxia, nystagmus, dysarthria, confusion, and seizures
– Fine tremor can occur in therapeutic range, but becomes coarser in toxicity
– If allowed to progress, toxicity can result in coma with hyperreflexia and increased tone, and irreversible neurological damage
– Treatment is supportive, with attention to electrolytes, fluid balance, renal function, and seizure control
– Bowel irrigation can be used in significant recent overdose, diuretics should be avoided, and haemodialysis may be required
– Benzodiazepines can control agitation.

It is recommended to avoid using first generation H1 antihistamines such as chlorpheniramine in individuals who drive of operate heavy machinery due to their ability to easily penetrate the blood brain barrier and cause sedation.

Antihistamines: Types and Uses

Antihistamines are drugs that block the effects of histamine, a neurotransmitter that regulates physiological function in the gut and potentiates the inflammatory and immune responses of the body. There are two types of antihistamines: H1 receptor blockers and H2 receptor blockers. H1 blockers are mainly used for allergic conditions and sedation, while H2 blockers are used for excess stomach acid.

There are also first and second generation antihistamines. First generation antihistamines, such as diphenhydramine and promethazine, have uses in psychiatry due to their ability to cross the blood brain barrier and their anticholinergic properties. They tend to be sedating and are useful for managing extrapyramidal side effects. Second generation antihistamines, such as loratadine and cetirizine, show limited penetration of the blood brain barrier and are less sedating.

It is important to note that there are contraindications to first-generation antihistamines, including benign prostatic hyperplasia, angle-closure glaucoma, and pyloric stenosis in infants. These do not apply to second-generation antihistamines.

Individuals of African and African-American descent exhibit the greatest prevalence of deficient CYP2D6 metabolism, resulting in a higher likelihood of being poor metabolisers. Codeine is classified as a prodrug, necessitating initial metabolism (specifically by CYP2D6) before it can produce pain-relieving effects.

The Cytochrome P450 system is a group of enzymes that metabolize drugs by altering their functional groups. The system is located in the liver and small intestine and is involved in drug interactions through enzyme induction of inhibition. Notable inducers include smoking, alcohol, and St John’s Wort, while notable inhibitors include grapefruit juice and some SSRIs. CYP2D6 is important due to genetic polymorphism, and CYP3A4 is the most abundant subfamily and is commonly involved in interactions. Grapefruit juice inhibits both CYP1A2 and CYP3A4, while tobacco smoking induces CYP1A2. The table summarizes the main substrates, inhibitors, and inducers for each CYP enzyme.

Antipsychotics can be classified in different ways, with the most common being typical (first generation) and atypical (second generation) types. Typical antipsychotics block dopamine (D2) receptors and have varying degrees of M1, Alpha-1, and H1 receptor blockade. Atypical antipsychotics have a lower propensity for extrapyramidal side-effects and are attributed to the combination of relatively lower D2 antagonism with 5HT2A antagonism. They are also classified by structure, with examples including phenothiazines, butyrophenones, thioxanthenes, diphenylbutylpiperidine, dibenzodiazepines, benzoxazoles, thienobenzodiazepine, substituted benzamides, and arylpiperidylindole (quinolone). Studies have found little evidence to support the superiority of atypicals over typicals in terms of efficacy, discontinuation rates, of adherence, with the main difference being the side-effect profile. The Royal College also favors classification by structure.

Understanding the Volume of Distribution in Pharmacology

The volume of distribution (Vd) is a crucial concept in pharmacology that helps determine how a drug distributes in the body. It is also known as the apparent volume of distribution, as it is an abstract volume. The Vd indicates whether a drug concentrates in the plasma of spreads out in the body. Drugs that are highly polar tend to stay in central compartments such as the plasma, resulting in a low Vd. Conversely, drugs that are more lipid-soluble are distributed widely, such as in fat, resulting in a high Vd.

The Vd is calculated by dividing the amount of drug in the body by the concentration in the plasma. Clinically, the Vd is used to determine the loading dose of a drug required for a desired blood concentration and to estimate blood concentration in the treatment of overdose. The units of Vd are in volume.

The apparent volume of distribution is dependent on the drug’s lipid of water solubility, plasma protein binding, and tissue binding. Plasma protein binding affects the Vd, as drugs that bind to plasma proteins like albumin have a smaller apparent volume of distribution. This is because they are extracted from plasma and included in drug concentration measurements, which can give a misleading impression of their volume of distribution. Understanding the Vd is essential in pharmacology to ensure the safe and effective use of drugs.

Torsades de pointes may not be present on an ECG even if the patient experiences recurring episodes, as it has a tendency to appear and disappear.

QTc Prolongation: Risks and Identification

The QT interval is a measure of the time it takes for the ventricles to repolarize and is calculated from the beginning of the QRS complex to the end of the T wave. However, the QT interval varies with the heart rate, making it difficult to use a single number as a cut-off for a prolonged QT. Instead, a corrected QT interval (QTc) is calculated for each heart rate using various formulas. A QTc over the 99th percentile is considered abnormally prolonged, with approximate values of 470 ms for males and 480 ms for females.

Prolonged QT intervals can lead to torsade de pointes (TdP), a polymorphic ventricular tachycardia that can be fatal if it degenerates into ventricular fibrillation. TdP is characterized by a twisting of the QRS complexes around an isoelectric line and is often asymptomatic but can also be associated with syncope and death. An accurate diagnosis requires an ECG to be recorded during the event. It is important to note that an increase in the QT interval due to a new conduction block should not be considered indicative of acquired LQTS and risk for TdP.

Antipsychotic drugs are known to cause weight gain, but some more than others. The reason for this is not due to a direct metabolic effect, but rather an increase in appetite and a decrease in activity levels. The risk of weight gain appears to be linked to clinical response. There are several suggested mechanisms for this, including antagonism of certain receptors and hormones that stimulate appetite. The risk of weight gain varies among different antipsychotics, with clozapine and olanzapine having the highest risk. Management strategies for antipsychotic-induced weight gain include calorie restriction, low glycemic index diet, exercise, and switching to an alternative antipsychotic. Aripiprazole, ziprasidone, and lurasidone are recommended as alternative options. Other options include aripiprazole augmentation, metformin, orlistat, liraglutide, and topiramate.

ADHD medications can be classified into stimulant and non-stimulant drugs. The therapeutic effects of these drugs are believed to be mediated through the action of noradrenaline in the prefrontal cortex. Common side effects of these drugs include decreased appetite, insomnia, nervousness, headache, and nausea. Stimulant drugs like dexamphetamine, methylphenidate, and lisdexamfetamine inhibit the reuptake of dopamine and noradrenaline. Non-stimulant drugs like atomoxetine, guanfacine, and clonidine work by increasing noradrenaline levels in the synaptic cleft through different mechanisms. The most common side effects of these drugs are decreased appetite, somnolence, headache, and abdominal pain.

Nocturia is often the first indication of nephrogenic diabetes insipidus, which can occur in 20-40% of patients who take lithium for an extended period. This condition can cause a gradual decrease in the GFR, which may be reversible in the early stages. If muscle mass is reduced of the diet is low in protein, the serum creatinine level may be normal of near-normal.

Hyperparathyroidism is not a likely cause because although 15-20% of long-term lithium users may have elevated calcium levels, only a few will experience hyperparathyroidism symptoms.

Syndrome of inappropriate ADH secretion is not associated with lithium therapy and would not present with polyuria of renal impairment.

Tubulointerstitial nephritis is a rare complication of lithium therapy.

Water intoxication would cause polyuria of dilutional hyponatremia, but not renal impairment.

Alternative Routes of Administration for Antidepressants

While most antidepressants are taken orally, there are a few alternative routes of administration available. However, it is important to note that these non-oral preparations should only be used when absolutely necessary, as they may not have a UK licence.

One effective alternative route is sublingual administration of fluoxetine liquid. Buccal administration of selegiline is also available. Crushed amitriptyline has been shown to be effective when administered via this route.

Intravenous administration is another option, with several antidepressants available in IV preparations, including citalopram, escitalopram, mirtazapine, amitriptyline, clomipramine, and allopregnanolone (which is licensed in the US for postpartum depression). Ketamine has also been shown to be effective when administered intravenously.

Intramuscular administration of flupentixol has been shown to have a mood elevating effect, but amitriptyline was discontinued as an IM preparation due to the high volumes required.

Transdermal administration of selegiline is available, and suppositories containing amitriptyline, clomipramine, imipramine, and trazodone have been manufactured by pharmacies, although there is no clear data on their effectiveness. Sertraline tablets and doxepin capsules have also been given rectally.

ADHD medications can be classified into stimulant and non-stimulant drugs. The therapeutic effects of these drugs are believed to be mediated through the action of noradrenaline in the prefrontal cortex. Common side effects of these drugs include decreased appetite, insomnia, nervousness, headache, and nausea. Stimulant drugs like dexamphetamine, methylphenidate, and lisdexamfetamine inhibit the reuptake of dopamine and noradrenaline. Non-stimulant drugs like atomoxetine, guanfacine, and clonidine work by increasing noradrenaline levels in the synaptic cleft through different mechanisms. The most common side effects of these drugs are decreased appetite, somnolence, headache, and abdominal pain.

This is a case of neuroleptic malignant syndrome, which is primarily associated with the use of antipsychotic medications. The key features of NMS include mental status changes, muscular rigidity, hyperthermia, and autonomic instability, typically presenting as tachycardia. Mental state changes are often the first symptom to appear.

Serotonin Syndrome and Neuroleptic Malignant Syndrome are two conditions that can be difficult to differentiate. Serotonin Syndrome is caused by excess serotonergic activity in the CNS and is characterized by neuromuscular abnormalities, altered mental state, and autonomic dysfunction. On the other hand, Neuroleptic Malignant Syndrome is a rare acute disorder of thermoregulation and neuromotor control that is almost exclusively caused by antipsychotics. The symptoms of both syndromes can overlap, but there are some distinguishing clinical features. Hyper-reflexia, ocular clonus, and tremors are more prominent in Serotonin Syndrome, while Neuroleptic Malignant Syndrome is characterized by uniform ‘lead-pipe’ rigidity and hyporeflexia. Symptoms of Serotonin Syndrome usually resolve within a few days of stopping the medication, while Neuroleptic Malignant Syndrome can take up to 14 days to remit with appropriate treatment. The following table provides a useful guide to the main differentials of Serotonin Syndrome and Neuroleptic Malignant Syndrome.

Antipsychotic drugs are known to cause weight gain, but some more than others. The reason for this is not due to a direct metabolic effect, but rather an increase in appetite and a decrease in activity levels. The risk of weight gain appears to be linked to clinical response. There are several suggested mechanisms for this, including antagonism of certain receptors and hormones that stimulate appetite. The risk of weight gain varies among different antipsychotics, with clozapine and olanzapine having the highest risk. Management strategies for antipsychotic-induced weight gain include calorie restriction, low glycemic index diet, exercise, and switching to an alternative antipsychotic. Aripiprazole, ziprasidone, and lurasidone are recommended as alternative options. Other options include aripiprazole augmentation, metformin, orlistat, liraglutide, and topiramate.