According to the Maudsley Guidelines, haloperidol causes the greatest increase in QTc interval among antipsychotic medications. It is important for men to have a QTc interval below 440 ms and women below 470 ms. While aripiprazole and paliperidone have not been proven to cause an increase in QTc interval, other antipsychotics, including atypical drugs like quetiapine, can have moderate to significant effects. A prolonged QTc interval, especially above 500ms, is associated with sudden cardiac death. Diazepam and other benzodiazepines have no effect on QTc interval, while amisulpride has a low effect. Citalopram is the only SSRI that has a low effect on QTc interval. Although erythromycin and other antibiotics can have an effect on QTc interval, the question specifically asks about psychotropic medications.

Cytochrome P450 is an important enzyme system involved in drug metabolism. Certain substances can either increase or decrease the activity of this system. Smoking, alcohol, barbiturates, carbamazepine, Phenytoin, and St John’s Wort are known to induce the activity of cytochrome P450. On the other hand, chlorpromazine, selective serotonin reuptake inhibitors (SSRIs), and grapefruit juice are known to inhibit the activity of cytochrome P450.

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.

Nalmefene (Selincro) is a medication that was licensed in 2013 for the treatment of alcohol misuse, particularly in cases where abstinence is not a feasible goal. It is classified as an opioid receptor antagonist of opioid system modulator and is the first new medication for alcohol misuse in the UK in over a decade. Acamprosate has been available in Europe since around 1989 and is licensed as a treatment for alcohol dependence. Chlormethiazole (Heminevrin) was previously widely used in managing alcohol withdrawal. Disulfiram (Antabuse) is an aversive therapy that has been used for a long time to treat alcohol misuse of dependence. Naltrexone, like Nalmefene, is an opioid receptor antagonist and has been licensed for managing alcohol dependence since approximately 1994.

Anticholinergic side effects such as dry mouth, blurred vision, and urinary retention are commonly observed with the use of first generation H1 antihistamines like diphenhydramine.

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.

Maudsley Guidelines: Dystonia

Dystonia is a type of adverse reaction that can occur in patients taking typical antipsychotics. It is characterized by symptoms such as torticollis and oculogyric spasm. About 10% of patients who are exposed to these medications may develop acute dystonia. This reaction is more likely to occur in the early stages of treatment of after a dose increase. Additionally, it can also happen when the patient stops taking the drug. Therefore, it is important to monitor patients closely for signs of dystonia and adjust the medication as needed.

Extrapyramidal side-effects (EPSE’s) are a group of side effects that affect voluntary motor control, commonly seen in patients taking antipsychotic drugs. EPSE’s include dystonias, parkinsonism, akathisia, and tardive dyskinesia. They can be frightening and uncomfortable, leading to problems with non-compliance and can even be life-threatening in the case of laryngeal dystonia. EPSE’s are thought to be due to antagonism of dopaminergic D2 receptors in the basal ganglia. Symptoms generally occur within the first few days of treatment, with dystonias appearing quickly, within a few hours of administration of the first dose. Newer antipsychotics tend to produce less EPSE’s, with clozapine carrying the lowest risk and haloperidol carrying the highest risk. Akathisia is the most resistant EPSE to treat. EPSE’s can also occur when antipsychotics are discontinued (withdrawal dystonia).

Out of the given options, amisulpride is the most suitable medication as it is not extensively metabolized by the liver. However, it should be avoided in individuals with established renal failure as a normal glomerular filtration rate is considered to be >90 ml/min/1.73m2.

Hepatic Impairment: Recommended Drugs

Patients with hepatic impairment may experience reduced ability to metabolize drugs, toxicity, enhanced dose-related side effects, reduced ability to synthesize plasma proteins, and elevated levels of drugs subject to first-pass metabolism due to reduced hepatic blood flow. The Maudsley Guidelines 14th Ed recommends the following drugs for patients with hepatic impairment:

Antipsychotics: Paliperidone (if depot required), Amisulpride, Sulpiride

Antidepressants: Sertraline, Citalopram, Paroxetine, Vortioxetine (avoid TCA and MAOI)

Mood stabilizers: Lithium

Sedatives: Lorazepam, Oxazepam, Temazepam, Zopiclone 3.75mg (with care)

Extrapyramidal side-effects (EPSE’s) are a group of side effects that affect voluntary motor control, commonly seen in patients taking antipsychotic drugs. EPSE’s include dystonias, parkinsonism, akathisia, and tardive dyskinesia. They can be frightening and uncomfortable, leading to problems with non-compliance and can even be life-threatening in the case of laryngeal dystonia. EPSE’s are thought to be due to antagonism of dopaminergic D2 receptors in the basal ganglia. Symptoms generally occur within the first few days of treatment, with dystonias appearing quickly, within a few hours of administration of the first dose. Newer antipsychotics tend to produce less EPSE’s, with clozapine carrying the lowest risk and haloperidol carrying the highest risk. Akathisia is the most resistant EPSE to treat. EPSE’s can also occur when antipsychotics are discontinued (withdrawal dystonia).

Antidepressants can cause discontinuation symptoms when patients stop taking them, regardless of the type of antidepressant. These symptoms usually occur within 5 days of stopping the medication and can last up to 3 weeks. Symptoms include flu-like symptoms, dizziness, insomnia, vivid dreams, irritability, crying spells, and sensory symptoms. SSRIs and related drugs with short half-lives, such as paroxetine and venlafaxine, are particularly associated with discontinuation symptoms. Tapering antidepressants at the end of treatment is recommended to prevent these symptoms. TCAs and MAOIs are also associated with discontinuation symptoms, with amitriptyline and imipramine being the most common TCAs and all MAOIs being associated with prominent discontinuation symptoms. Patients at highest risk for discontinuation symptoms include those on antidepressants with shorter half-lives, those who have been taking antidepressants for 8 weeks of longer, those using higher doses, younger people, and those who have experienced discontinuation symptoms before. Agomelatine is not associated with any discontinuation syndrome. If a discontinuation reaction occurs, restarting the antidepressant of switching to an alternative with a longer half-life and tapering more slowly may be necessary. Explanation and reassurance are often sufficient for mild symptoms. These guidelines are based on the Maudsley Guidelines 14th Edition and a study by Tint (2008).

Elevated troponin levels typically manifest within a few hours of myocardial injury and persist for a maximum of two weeks.

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.

Prescribing in the Elderly: Iatrogenic Consequences

Many medications, both prescribed and over-the-counter, can have significant adverse effects in the elderly population. It is important to note that the lists provided below are not exhaustive, and only the most common and important examples are given.

Medications Linked to Delirium and Other Cognitive Disorders

Medications are the most common reversible cause of delirium and dementia in the elderly. Many medications can cause cognitive impairment, but the classes of drugs most strongly associated with the development of drug-induced dementia are opioids, benzodiazepines, and anticholinergics.

According to a systematic review done in 2011 (Clegg, 2011), long-acting benzodiazepines (e.g., diazepam) are more troublesome than those that are shorter-acting. Opioids are associated with an approximately 2-fold increased risk of delirium in medical and surgical patients (Clegg, 2011). Pethidine appears to have a higher risk of delirium compared with other members of the opioid class. This may be because pethidine can accumulate when renal function is impaired and is converted to a metabolite with anticholinergic properties.

Some antipsychotic drugs have considerable antimuscarinic (anticholinergic) activity (e.g., chlorpromazine and clozapine), which may cause of worsen delirium. Delirium is uncommon in newer antipsychotics (but has been reported).

Medications Linked to Mood Changes

The following medications are well known to precipitate mood changes:

– Centrally-acting antihypertensives (e.g., methyldopa, reserpine, and clonidine) can cause depressive symptoms.
– Interferon-a is capable of inducing depressive symptoms.
– Digoxin is capable of inducing depressive symptoms.
– Corticosteroids can cause depressive, manic, and mixed symptoms with of without psychosis.
– Antidepressants can precipitate mania.

Medications Linked to Psychosis

The following medications are well known to precipitate psychosis:

– Anti-Parkinson’s Medications (e.g., bromocriptine, amantadine, selegiline, anticholinergics (e.g., trihexyphenidyl, benztropine, benzhexol), and levodopa).
– Corticosteroids

Medications Linked to Anxiety

The following medications are well known to precipitate anxiety:

– Stimulants
– β adrenergic inhalers

The preferred initial treatment for alcohol withdrawal syndrome is benzodiazepines.

The information provided is valuable because the CATIE study was conducted in a real-world setting, making the estimate potentially applicable to the UK.

CATIE Study: Comparing Antipsychotic Medications for Schizophrenia Treatment

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study, funded by the National Institute of Mental Health (NIMH), was a nationwide clinical trial that aimed to compare the effectiveness of older and newer antipsychotic medications used to treat schizophrenia. It is the largest, longest, and most comprehensive independent trial ever conducted to examine existing therapies for schizophrenia. The study consisted of two phases.

Phase I of CATIE compared four newer antipsychotic medications to one another and an older medication. Participants were followed for 18 months to evaluate longer-term patient outcomes. The study involved over 1400 participants and was conducted at various treatment sites, representative of real-life settings where patients receive care. The results from CATIE are applicable to a wide range of people with schizophrenia in the United States.

The medications were comparably effective, but high rates of discontinuation were observed due to intolerable side-effects of failure to adequately control symptoms. Olanzapine was slightly better than the other drugs but was associated with significant weight gain as a side-effect. Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications. Movement side effects primarily associated with the older medications were not seen more frequently with perphenazine than with the newer drugs.

Phase II of CATIE sought to provide guidance on which antipsychotic to try next if the first failed due to ineffectiveness of intolerability. Participants who discontinued their first antipsychotic medication because of inadequate management of symptoms were encouraged to enter the efficacy (clozapine) pathway, while those who discontinued their first treatment because of intolerable side effects were encouraged to enter the tolerability (ziprasidone) pathway. Clozapine was remarkably effective and was substantially better than all the other atypical medications.

The CATIE study also looked at the risk of metabolic syndrome (MS) using the US National Cholesterol Education Program Adult Treatment Panel criteria. The prevalence of MS at baseline in the CATIE group was 40.9%, with female patients being three times as likely to have MS compared to matched controls and male patients being twice as likely.

Hyponatremia in Psychiatric Patients

Hyponatremia, of low serum sodium, can occur in psychiatric patients due to the disorder itself, its treatment, of other medical conditions. Symptoms include nausea, confusion, seizures, and muscular cramps. Drug-induced hyponatremia is known as the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), which results from excessive secretion of ADH and fluid overload. Diagnosis is based on clinically euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality. SSRIs, SNRIs, and tricyclics are the most common drugs that can cause SIADH. Risk factors for SIADH include starting a new drug, and treatment usually involves fluid restriction and sometimes demeclocycline.

According to Gillman (1998), it is recommended to avoid using the antihistamines brompheniramine and chlorpheniramine as they act as serotonin reuptake inhibitors (SRIs). However, all other antihistamines are considered safe for use. Gillman’s study focused on the history and risk of serotonin syndrome.

MAOIs: A Guide to Mechanism of Action, Adverse Effects, and Dietary Restrictions

First introduced in the 1950s, MAOIs were the first antidepressants introduced. However, they are not the first choice in treating mental health disorders due to several dietary restrictions and safety concerns. They are only a treatment option when all other medications are unsuccessful. MAOIs may be particularly useful in atypical depression (over eating / over sleeping, mood reactivity).

MAOIs block the monoamine oxidase enzyme, which breaks down different types of neurotransmitters from the brain: norepinephrine, serotonin, dopamine, as well as tyramine. There are two types of monoamine oxidase, A and B. The MOA A are mostly distributed in the placenta, gut, and liver, but MOA B is present in the brain, liver, and platelets. Selegiline and rasagiline are irreversible and selective inhibitors of MAO type B, but safinamide is a reversible and selective MAO B inhibitor.

The most common adverse effects of MAOIs occurring early in treatment are orthostatic hypotension, daytime sleepiness, insomnia, and nausea; later common effects include weight gain, muscle pain, myoclonus, paraesthesia, and sexual dysfunction.

Pharmacodynamic interactions with MAOIs can cause two types of problem: serotonin syndrome (mainly due to SSRIs) and elevated blood pressure (caused by indirectly acting sympathomimetic amines releasers, like pseudoephedrine and phenylephrine). The combination of MAOIs and some TCAs appears safe. Only those TCAs with significant serotonin reuptake inhibition (clomipramine and imipramine) are likely to increase the risk of serotonin syndrome.

Tyramine is a monoamine found in various foods, and is an indirect sympathomimetic that can cause a hypertensive reaction in patients receiving MAOI therapy. For this reason, dietary restrictions are required for patients receiving MAOIs. These restrictions include avoiding matured/aged cheese, fermented sausage, improperly stored meat, fava of broad bean pods, and certain drinks such as on-tap beer. Allowed foods include fresh cottage cheese, processed cheese slices, fresh packaged of processed meat, and other alcohol (no more than two bottled or canned beers of two standard glasses of wine, per day).

Agomelatine: A New Drug for Depression Treatment

Agomelatine is a recently developed medication that is used to treat depression. Its mechanism of action involves acting as an agonist at melatonin M1 and M2 receptors, while also acting as an antagonist at 5HT2C receptors. The effects of melatonin appear to promote sleep, while the 5HT2C antagonism leads to the release of dopamine and norepinephrine in the frontal cortex. Interestingly, serotonin levels do not appear to be affected by this medication.

Anabolic Steroids: Uses, Misuse, and Complications

Anabolic steroids are synthetic derivatives of testosterone that have both anabolic and androgenic properties. They are commonly used by athletes to enhance performance and by individuals to improve physical appearance. However, their misuse is not uncommon, with nearly half of users of dedicated bodybuilding gyms admitting to taking anabolic agents. Misuse can lead to dependence, tolerance, and the development of psychiatric disorders such as aggression, psychosis, mania, and depression/anxiety.

There are three common regimes practised by steroid misusers: ‘cycling’, ‘stacking’ and ‘pyramiding’. Anabolic steroids can be taken orally, injected intramuscularly, and applied topically in the form of creams and gels. Other drugs are also used by athletes, such as clenbuterol, ephedrine, thyroxine, insulin, tamoxifen, human chorionic Gonadotropin, diuretics, and growth hormone.

Medical complications are common and can affect various systems, such as the musculoskeletal, cardiovascular, hepatic, reproductive (males and females), dermatological, and other systems. Complications include muscular hypertrophy, increased blood pressure, decreased high-density lipoprotein cholesterol and increased low-density lipoprotein cholesterol, cholestatic jaundice, benign and malignant liver tumours, testicular atrophy, sterility, gynaecomastia, breast tissue shrinkage, menstrual abnormalities, masculinisation, male-pattern baldness, acne, sleep apnoea, exacerbation of tic disorders, polycythaemia, altered immunity, and glucose intolerance.

Anabolic steroids are a class C controlled drug and can only be obtained legally through a medical prescription. It is important to educate individuals about the risks and complications associated with their misuse and to promote safe and legal use.

The Maudsley Guidelines recommend the use of diazepam and clonazepam in their treatment plan for antipsychotic induced akathisia, likely because of their extended duration of action.

Benzodiazepines are a class of drugs commonly used to treat anxiety and sleep disorders. It is important to have a working knowledge of the more common benzodiazepines and their half-life. Half-life refers to the amount of time it takes for half of the drug to be eliminated from the body.

Some of the more common benzodiazepines and their half-life include diazepam with a half-life of 20-100 hours, clonazepam with a half-life of 18-50 hours, chlordiazepoxide with a half-life of 5-30 hours, nitrazepam with a half-life of 15-38 hours, temazepam with a half-life of 8-22 hours, lorazepam with a half-life of 10-20 hours, alprazolam with a half-life of 10-15 hours, oxazepam with a half-life of 6-10 hours, zopiclone with a half-life of 5-6 hours, zolpidem with a half-life of 2 hours, and zaleplon with a half-life of 2 hours. Understanding the half-life of these drugs is important for determining dosages and timing of administration.

Extrapyramidal side-effects (EPSE’s) are a group of side effects that affect voluntary motor control, commonly seen in patients taking antipsychotic drugs. EPSE’s include dystonias, parkinsonism, akathisia, and tardive dyskinesia. They can be frightening and uncomfortable, leading to problems with non-compliance and can even be life-threatening in the case of laryngeal dystonia. EPSE’s are thought to be due to antagonism of dopaminergic D2 receptors in the basal ganglia. Symptoms generally occur within the first few days of treatment, with dystonias appearing quickly, within a few hours of administration of the first dose. Newer antipsychotics tend to produce less EPSE’s, with clozapine carrying the lowest risk and haloperidol carrying the highest risk. Akathisia is the most resistant EPSE to treat. EPSE’s can also occur when antipsychotics are discontinued (withdrawal dystonia).

Rivastigmine inhibits cholinesterase in a reversible manner.

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.

Weight gain is a common side effect of antipsychotic medications, which may be caused by various mechanisms such as 5HT2c and H1 antagonism, hyperprolactinaemia, and increased serum leptin. This weight gain is often due to increased food intake and reduced energy expenditure. Additionally, antipsychotic-induced weight gain can lead to diabetes mellitus, with females being more susceptible to metabolic side effects than males. Among antipsychotics, clozapine and olanzapine have the highest risk of weight gain, while quetiapine and risperidone have a moderate risk. On the other hand, aripiprazole, asenapine, and amisulpride (the 3 As) are associated with the least amount of weight gain.

A drug in depot form is released slowly.

Depot antipsychotics (long-term injectables) are available for both first-generation and second-generation antipsychotics. The efficacy of first-generation antipsychotic depots is considered to be broadly similar, with zuclopenthixol potentially being more effective in preventing relapses but with an increased burden of adverse effects. Second-generation antipsychotic depots have a lower propensity for extrapyramidal symptoms compared to first-generation antipsychotic depots. Test doses should be administered for first-generation antipsychotic depots, and only gluteal injection is licensed for olanzapine depots. Post-injection syndrome is a potential adverse effect of olanzapine depots, which can cause significant weight gain. Patients may be most at risk of deterioration immediately after a depot rather than just before, and relapse seems to occur 3-6 months after withdrawing a depot.

The Significance of Active Metabolites in Drug Discovery and Development

Certain drugs are classified as prodrugs, which means that they are inactive when administered and require metabolism to become active. These drugs are converted into an active form, which is referred to as an active metabolite. Some drugs have important active metabolites, such as diazepam, dothiepin, fluoxetine, imipramine, risperidone, amitriptyline, and codeine, which are desmethyldiazepam, dothiepin sulfoxide, norfluoxetine, desipramine, 9-hydroxyrisperidone, nortriptyline, and morphine, respectively.

The role of pharmacologically active metabolites in drug discovery and development is significant. Understanding the active metabolites of a drug can help in the development of more effective and safer drugs. Active metabolites can also provide insights into the pharmacokinetics and pharmacodynamics of a drug, which can aid in the optimization of dosing regimens. Additionally, active metabolites can have different pharmacological properties than the parent drug, which can lead to the discovery of new therapeutic uses for a drug. Therefore, the study of active metabolites is an important aspect of drug discovery and development.

Mirtazapine works by blocking the activity of 5HT2 and 5HT3, H1, and alpha 1 receptors. These actions promote sleep, except for the alpha 2 receptor, which normally inhibits the release of norepinephrine. As the dosage of mirtazapine increases, its ability to enhance sleep may decrease due to its antagonism of the alpha 2 receptor. Therefore, doses of 30mg of less are typically used to treat insomnia. This information is from the book Foundations of Psychiatric Sleep Medicine, published by Cambridge University Press in 2011, on page 224.

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.

Toxicity in Overdose: Comparing MAOIs, SSRIs, Tricyclics, and Mirtazapine

When it comes to the risk of overdose, not all antidepressants are created equal. MAOIs (except for moclobemide) have a high toxicity level, with as little as 400 mg of phenelzine being potentially fatal. On the other hand, SSRIs are considered relatively safe in overdose. Tricyclics, except for lofepramine, have a higher risk of toxicity in overdose. However, lofepramine is relatively safe in overdose. Mirtazapine, while sedative, has a low risk of toxicity even in large doses, and may not produce any symptoms. It’s important to note that regardless of the perceived safety of a medication, any overdose should be taken seriously and medical attention should be sought immediately.

Antidepressants: Minimum Effective Doses

According to the Maudsley 13th, the following are the minimum effective doses for various antidepressants:

– Citalopram: 20 mg/day
– Fluoxetine: 20 mg/day
– Fluvoxamine: 50 mg/day
– Paroxetine: 20 mg/day
– Sertraline: 50 mg/day
– Mirtazapine: 30 mg/day
– Venlafaxine: 75 mg/day
– Duloxetine: 60 mg/day
– Agomelatine: 25 mg/day
– Moclobemide: 300 mg/day
– Trazodone: 150 mg/day

Note that these are minimum effective doses and may vary depending on individual factors and response to treatment. It is important to consult with a healthcare professional before starting of changing any medication regimen.

Lithium is well-known for causing various thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis.

EPSE’s have been linked to the use of fluoxetine, and all of the treatment options are utilized to address them.

Extrapyramidal side-effects (EPSE’s) are a group of side effects that affect voluntary motor control, commonly seen in patients taking antipsychotic drugs. EPSE’s include dystonias, parkinsonism, akathisia, and tardive dyskinesia. They can be frightening and uncomfortable, leading to problems with non-compliance and can even be life-threatening in the case of laryngeal dystonia. EPSE’s are thought to be due to antagonism of dopaminergic D2 receptors in the basal ganglia. Symptoms generally occur within the first few days of treatment, with dystonias appearing quickly, within a few hours of administration of the first dose. Newer antipsychotics tend to produce less EPSE’s, with clozapine carrying the lowest risk and haloperidol carrying the highest risk. Akathisia is the most resistant EPSE to treat. EPSE’s can also occur when antipsychotics are discontinued (withdrawal dystonia).

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.

Due to its short half-life of 6 hours, quetiapine is administered twice daily in divided doses. However, a modified release version called Seroquel XL is available, which can be taken once daily.

Antipsychotic Half-life and Time to Steady State

Antipsychotic medications are commonly used to treat various mental health conditions, including schizophrenia and bipolar disorder. Understanding the half-life and time to steady state of these medications is important for determining dosing and monitoring their effectiveness.

Aripiprazole has a half-life of 75 hours and takes approximately 2 weeks to reach steady state. Olanzapine has a half-life of 30 hours and takes about 1 week to reach steady state. Risperidone has a half-life of 20 hours when taken orally and takes 2-3 days to reach steady state. Clozapine and Amisulpride both have a half-life of 12 hours and take 2-3 days to reach steady state. Ziprasidone has a shorter half-life of 7 hours and takes 2-3 days to reach steady state. Quetiapine has the shortest half-life of 6 hours and also takes 2-3 days to reach steady state.

Knowing the half-life and time to steady state of antipsychotic medications can help healthcare providers determine the appropriate dosing and frequency of administration. It can also aid in monitoring the effectiveness of the medication and adjusting the treatment plan as needed.