Drugs used to Treat Antipsychotic-Induced Weight-Gain (Mnemonic)

The following mnemonic is for the drugs used to treat antipsychotic-induced weight gain. The list is not based on priority; however, metformin is the preferred choice, especially when there is comorbid polycystic ovary disease. Orlistat, with calorie restriction, is also an effective choice.

FORMAT-B

• Fluoxetine 
• Orlistat
• Reboxetine
• Metformin, methylcellulose, melatonin
• Topiramate
• Bupropion 

Drugs and Conditions which Affect Serum Lithium Levels

Question

Which one of the following may affect blood levels of lithium?

A. NSAIDS

B. ACE inhibitors

C. Thiazide diuretics

D. Dehydration

Differences between Typical and Atypical Antipsychotics: Efficacy and Adverse Effects

Typical Versus Atypical Antipsychotics

By definition, typical antipsychotics are those which produce extrapyramidal side effects, while atypical antipsychotics do not. However, at the doses used today, most atypical antipsychotics do not produce extrapyramidal side effects. Whether typical and atypical antipsychotics differ in efficacy in a long-held debate. Except for clozapine, there are no significant differences in the efficacy of typical and atypical antipsychotics. 

Two large pragmatic studies, CATIE in the United States, and CutLASS in the United Kingdom, in 2005 and 2006, respectively, produced similar conclusions. Another meta-analysis, in 2009 showed that risperidone, olanzapine, and amisulpride were more effective compared to typical antipsychotics. 

Overall, typical antipsychotics are more likely to produce extrapyramidal side effects, while atypical ones are more likely to produce metabolic side effects, including weight gain, hyperlipemia, and diabetes. 

Clozapine is more effective than both typical and other atypical antipsychotics. 

Clinical Vignette: Preventing Complication in A Man with Agitation

A 30-year-old man, who is a heavy alcohol drinker, presented to the emergency department with agitation, altered sensorium, marked tremors, visual hallucinations. On assessment, he is unaware of the time, place, and person. His blood pressure and pulse were 160/11 and 115/min on arrival but fluctuated on monitoring. A GP had given him haloperidol IM and diazepam IV to control his behavioral disturbance. 

What treatment-complication could arise?

a)       Seizures
b)      Over-sedation
c)       Respiratory depression
d)      Arrhythmia
e)       Worsening agitation

Benzodiazepines for the Treatment of Catatonia
Safest Treatment Option for Delirium Tremens
WHO Alcohol Withdrawal Treatment Guidelines

Interactions of Clozapine

The cytochrome P450 system of enzymes in the liver inactivates and removes the toxic substances, including drugs, from the body. These enzymes include CYP 2D6, 2C9, 2C19, and 1 A2. But certain drugs can inhibit or induce these enzymes themselves. Some SSRIs are potent inhibitors of an individual or multiple hepatic cytochrome P450 (CYP) pathways and the magnitude of these effects is dose-related. Several clinically significant drug interactions can, therefore, be predicted. For example, fluvoxamine is a potent inhibitor of CYP1A2 which can result in increased theophylline serum levels, fluoxetine is a potent inhibitor of CYP2D6 which can cause increased seizure risk with clozapine, and paroxetine is a potent inhibitor of CYP2D6 which can cause treatment failure with tamoxifen (a prodrug), leading to increased mortality. Escitalopram has the least impact on these enzymes.

QID: 20200407130027659

The Safest NSAID for a patient on lithium

What is the most suitable non-steroidal anti-inflammatory drug (NSAID) you can prescribe to a patient who is on Lithium therapy?

>> Aspirin or Sulindac. 

Lithium

 

Lithium

FAQ 01

What are the indications for lithium?

We use lithium in the prophylaxis and treatment of mania, prophylaxis of bipolar disorder, as an augmentation strategy for patients with treatment-resistant depression.

What are the common signs of lithium toxicity?

Thirst, polyuria, memory problems, tremor, weight gain, tiredness, diarrhea. Cognitive dysfunction is the most common symptom that leads to non-compliance. Side effects are dose-related.

What is the concentration at which toxic effects reliably occur?

Toxic effects reliably occur at 1.5mmol/l but toxic effects can occur at MUCH LOWER LEVELS in many patients, especially in older patients, systemically ill patients, and in use of alcohol or other CNS active meds

What are the two systems lithium causes the most damage to?

Thyroid and kidneys

What are the differences between the brands of lithium?

There are differences in bioavailability, and recommendations are to keep to the patient on the same brand. If it is necessary to change formulations, lithium levels must be monitored closely until a patient reaches a steady state.

What are the distinct forms of lithium found in different formulations?

Tablets have lithium carbonate; liquid has lithium citrate.

How is lithium administered, timing-wise?

We give it as a single daily dose at night. 

When should blood for serum lithium estimation be taken?

12 hours after the last dose. IF you're on liquid then you take the blood before the morning dose.

What can cause increased lithium concentrations?

A low-salt diet, diarrhoea, vomiting, excessive sweating, systemic illness of any origin, renal impairment, NSAIDs, ACE inhibitors, ARBs, diuretics.

Tell me about lithium and surgery?

Lithium is probably safe in minor surgery but is usually discontinued before major procedures and restarted once electrolytes normalize. The following points should be considered if you will take lithium during the period. Lithium prolongs the action of muscle relaxant, electrolyte imbalance can precipitate lithium toxicity, dehydration can too. increased, increased arrhythmia

What is your dose determined by?

Blood levels.

What is the therapeutic range of lithium?

0.4 to 1 mmol/l

What kind of damage does lithium cause to the thyroid?

It can cause both hyper and hypothyroidism.

What is lithium's lag phase?

5–7 days

What are the neurochemical effects of lithium?

It enhances serotonergic activity, reduces cholinergic activity, and inhibits PI and cAMP.

How is lithium transported across the cell membrane?

It is actively transported across membranes using a voltage-sensitive sodium channel and sodium-potassium ATPase.

Tell me about lithium and signal transduction?

It increases inositol monophosphate. It depletes free inositol. Adrenergic, cholinergic, serotonergic, and dopaminergic receptors are coupled to Pi turnover in the CNS. There is possibly a compensatory stabilization of biogenic amine imbalance. cAMP accumulation is inhibited. All of this is mediated by G proteins. Chronically, it may have effects through protein kinase C and expression of neuromodulators and components of secondary messenger systems.

Tell me about lithium's mechanism of action?

It affects serotonin precursor uptake, synthesis, release, storage, catabolism, receptors, and receptor effector interaction primarily presynaptically. It increases DA turnover, decreases DA formation, decreases striatal DA activity. Facilitates the release of NA through presynaptic autoreceptor. Stimulates Ach synthesis and release.

What percentage of people relapse when on lithium? What percentage relapse on a placebo?

34% relapse on lithium while 81% relapse on placebo.

What percentage relapse and after abrupt termination of lithium?

50% relapse within 5 months.

What can reduce the risk of relapse when you stop the lithium?

Tapering slowly

What percentage of bipolar patients will show an inadequate response to lithium alone and will require the addition of ADT or anticonvulsant?

50%

What patterns of bipolar show reduced the efficacy of lithium?

Rapid cyclers or mixed states. Personality disorders and substance abuse are also associated with poorer response.

Is MDI better or DMI better in lithium treatment?

MDI pattern which is preceding depression responds better to lithium while DMI which is when you get severe episodes of depression don’t respond as well.

How long does lithium take to work in bipolar depression?

3–4 weeks

What percentage of bipolar patients respond to lithium as an antidepressant vs how many unipolar patients respond to it as an antidepressant?

79% of bipolar patients and 36% of unipolar patients.

What percentage of treatment-refractory patients respond to lithium augmentation?

50%

What other ailments is lithium used to treat?

Schizoaffective disorders, cluster headache, preliminary use in HIV treated patients with zidovudine.

Give me the side effects of lithium by the system?

Neuromuscular: fine tremor, slowed cognition. GI: Nausea, diarrhea, weight gain. Thyroid: hypothyroid, hyperthyroid, raised TSH. Cardio: ST and T-wave changes, sinus Brady, T-wave depression. Renal: polyuria and polydipsia, diabetes insipidus, interstitial nephritis

Why does lithium cause organic damage?

Because of its accumulation and action of lithium on ion transport, second messenger, and receptor signaling systems.

Tell me all about lithiums damage to the thyroid?

It inhibits hormone synthesis and releases and inhibits the action of TSH. TSH induced hypothyroidism occurs between 5–35%. More common in females, 30% have elevated TFTs.

Give me lithium's important drug interactions?

Diuretics (loops<thiazide) increase lithium levels. Caffeine discontinuation can increase levels of NSAIDs to reduce Li clearance. Neuroleptics plus lithium worsen EPSEs.

What teratogenic effects does lithium have?

It has teratogenic effects on the cardiovascular system in the first trimester. Ebstein's anomaly.

What levels do you want lithium at?

0.6–0.8 in maintenance level 0.8–1.2 in an acute manic state.

How do you introduce lithium?

400–600mg given at night, increased weekly depending on serum monitoring to a maximum of 2g.

Describe the monitoring of lithium?

Check lithium level seven days after starting and seven days after each change of dose. Take blood samples 12 hours post-dose. Once the therapeutic serum level has been reached, continue to check lithium level/eGFR every three months and TFTs every six months. Keep an eye on the weight!

What are the side effects of lithium?

Fine tremor, Sedation impaired coordination  GI disturbances polyuria (more urine) Polydipsia (more thirsty)

 What are Signs of toxicity?

Lack of appetite Diarrhoea and vomiting  Blurred vision Marked tremor Drowsiness and confusion Slurred speech

What are the Interactions?

Diuretics, NSAIDS, HAloperidol, carbamazepine , antidepressants , ACEi,s ARBSs

How to counsel a  Patient?

Carry lithium cards will need regular blood tests. Be way of buying otcs, speak to pharmacist Maintain fluid and sodium intake. Women of childbearing age should use contraception to stay on the same brand should only be initiated in secondary care 

Monitoring?

Having a serum lithium concentration took 12 hours after the first dose. routine serum lithium Concentration took after initiation and after each dose change until stable and then every three months.

What type of medication is lithium? 

Mood stabilizer 

What is lithium used to treat? 

Gold standard preferred treatment for mania. 

What is the normal lithium blood serum level? 

0.6 – 1.2 millimoles per litre (mmol/L).

What are the short term adverse effects of lithium? 

Polyuria and polydipsia weight gain nausea and vomiting fine tremor headache metallic taste lethargy acne. 

What are the long term adverse effects of lithium?

Hyper or hypothyroidism kidney problems mild cognitive impairment and memory problems. 

What are the long term adverse effects of lithium?

Hyper or hypothyroidism kidney problems, mild cognitive impairment and memory problems. 

Why do patients taking lithium need to stay hydrated?

Because lithium interferes with regulating water and sodium dehydration, which worsen thyroid and kidney problems , 

What lithium concentration may show lithium toxicity?

1.5–2.0millimoles per liter (mmol/L). Lithium toxicity can also happen in therapeutic ranges (esp in the elderly) 

What are the symptoms of lithium toxicity?

Blurred vision, Vomiting, and diarrhoea, Coarse tremor, Muscle weakness, Confusion, Sluggishness, Ataxia, Dysarthria.

How/when would you monitor lithium blood serum levels?

If lithium toxicity signs are clear 5 days after starting restarting changing dose weekly during acute treatment then every 3 months once mental state and lithium levels are stable 

What diet would someone with lithium be on?

Regular diet with normal sodium and adequate fluid intake 

What is the side effect of sodium valproate?

Alopecia (hair loss)

Adverse effects of lithium?

Polyuria, Polydipsia, Weight Gain and Edema, Metallic Taste, TREMORS, Orthostatic Hypotension

Lithium has what effect during pregnancy?

Teratogenic

Lithium and NSAIDs cannot be given because?

NSAIDS causes lithium, Toxicity.

Lithium causes GI upset and should be taken with?

Food

They must avoid what type of beverages?

Caffeinated drinks

To which class of medications does lithium belong?

It is a mood stabilizer.

What conditions is lithium used to treat?

Used to treat bipolar disorder. Reduces frequency and severity of mania. It helps relieve depression, but more effective in treating mania. It helps to reduce the risk of suicide. Stabilises mood.

How long does it take to see results?

Takes up two weeks before seeing results.

Why are the Blood tests regularly taken?

because of the effect on kidneys and thyroids.

 What is the mechanism of action of lithium?

Though lithium is an effective way to treat bipolar disorder, it is still not clear how it works exactly. But studies have shown lithium affects the excitatory neurotransmitter, glutamate. Lithium changes inward and outward currents of glutamate receptors to help the body keep a healthy level.

What is the route of administration of lithium?

Oral

Side Effects?

Headaches. Nausea. Diarrhea. Excessive Vomiting. Weakness or Muscle Fatigue Tremor. Ataxia. Muscle twitches. Seizures. Coma.

Acute and Chronic Toxicity Acute?

Intentionally or accidentally taking too much lithium Chronic. Taking Lithium every day for a lengthy period. 

Withdrawal Symptoms?

Studies have shown there are no withdrawal symptoms. There is usually no case of addiction when using lithium.

Schedule of drugs?

Not subjected to the controlled substances act, so not a federally scheduled drug.

What is the therapeutic range for lithium?

0.4 to 1 millimole per litter (mmol/l) is the normal therapeutic range. It is 0.8 to 1 millimoles per litter for acute episodes of mania or patients who have previously relapsed.

Can you enlist four tests for the monitoring of lithium?

Serum lithium concentration, renal function (baseline and every six months), cardiac function (before initiation and every six months, same for thyroid), thyroid function.

Lithium route of elimination?

It has a renal excretion, freely filtered at glomerulus with an eighty percent reabsorption rate. 

Enlist ten warning signs for lithium? 

Increasing Gastrointestinal (GI) disturbances (V&D)  Visual disturbances (e.g. blurred vision). central nervous system (CNS) disturbances (drowsiness, unsteadiness, confusion). Fine tremor (and worse)  incontinence, polyuria serum concentration over two millimoles per liter (mmol/L)  leading to seizures, coma, renal failure, arrhythmias, blood pressure changes, circulatory failure, sudden death, hypothyroidism renal dysfunction (polyuria and polydipsia) and benign intracranial hypertension (e.g. persistent headache and visual disturbance).

Enlist six counseling points for lithium?

See the doctor if any of the warning signs occur. Advise patients of staying on the same brand of lithium carbonate. Maintain constant water and salt intake (especially during hot weather and infection). Advise patients on interactions of lithium with over-the-counter (OTC) medications and to avoid alcohol. Do not stop lithium unless the doctor told you otherwise. 

List ten drugs that have increased risk of toxicity when lithium is comorbid with them?

Mainly any drugs that affect renal output: Angiotensin-converting enzyme (ACE) inhibitors, angiotensin-2 antagonists, loop diuretics, thiazides, Non-steroidal potassium-sparing diuretics, aldosterone antagonists, metronidazole, SSRIs, tricyclics. L.A.S.T. T.A.N. M.A.P.

With which drug, there is an increased risk of ventricular arrhythmias when lithium is given? 

Amiodarone

List five medications with which there is an increased risk of neurotoxicity when given with lithium alongside? 

Methyldopa, phenytoin, carbamazepine, diltiazem, verapamil MPCDV 

Increased risk of extrapyramidal side effects when lithium is given alongside these drugs? 

Clozapine, haloperidol, sulpiride, phenothiazines, risperidone, flupentixol, zuclopenthixol.  Mnemonic: CH(ie)FS  PR(e)Z

Safety of lithium in pregnancy? First, second, third trimester?

First trimester: Avoid due to teratogenicity, including cardiac abnormalities. Second and third trimester: Dose requirements are increased during the second and third trimesters, which return to normal after delivery.

Can mothers breastfeed while on lithium treatment?

lithium is present in breastmilk and can cause toxicity in the infant.

When should lithium concentration be monitored in regards to the last dose?

Twelve hours after the last dose.

How often should we carry out serum lithium tests when starting treatment?

Weekly after initiation and, after each dose change, weekly again.

How often should serum lithium be tested once a patient has achieved maintenance therapy?

Every three months, unless a patient develops the intercurrent disease, or has a significant change in sodium or fluid intake.

How should lithium be stopped?

Reduce gradually over four weeks to three months to lessen the risk of relapse.

What to do if the patient must stop lithium immediately, e.g. due to severe renal failure? 

Change to atypical antipsychotic or valproate.

Date: 02/06/2020

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