Drugs

Question 1

What are the main mechanisms of action for Valproate?

Answer 1

Inhibits GABA catabolism, reduces arachidonic acid turnover, activates ERK pathway, promotes BDNF, inhibits histone deacetylase, and blocks voltage-gated sodium channels.

Question 2

What are the formulations of Valproate available in the UK?

Answer 2

Sodium valproate, valproic acid (for epilepsy), and semi-sodium valproate (for acute mania).

Question 3

How do sodium valproate and semi-sodium valproate differ in dosing?

Answer 3

Sodium valproate requires about 10% higher dose due to extra sodium content.

Question 4

Is there a difference in efficacy between valproic acid, sodium valproate, and semi-sodium valproate?

Answer 4

No clear difference; however, studies show mixed results regarding duration of hospital stay.

Question 5

What is the recommended dosing frequency for sodium valproate CR (Epilim Chrono)?

Answer 5

Can be given once daily.

Question 6

What are the licensed indications for Valproate in psychiatric practice?

Answer 6

Mania, bipolar depression, prophylaxis of bipolar disorder; aggression (weak evidence).

Question 7

Which valproate formulation is licensed for acute mania?

Answer 7

Semi-sodium valproate.

Question 8

What is the response rate and NNT of Valproate in mania?

Answer 8

Response rate ~50%, NNT = 2–4.

Question 9

Is Valproate more effective than Lithium in acute mania?

Answer 9

Lithium is generally more effective overall; valproate is useful if lithium fails.

Question 10

What does NICE recommend for Valproate in bipolar disorder?

Answer 10

First-line for acute mania and prophylaxis, but NOT in women of childbearing potential.

Question 11

Can Valproate be used in bipolar depression?

Answer 11

Yes, with small to medium effect size; ranks 5th in 2020 meta-analysis.

Question 12

Is Valproate effective as maintenance in bipolar disorder?

Answer 12

RCTs show mixed evidence; may be less effective than lithium alone.

Question 13

What is the BALANCE study conclusion regarding Valproate?

Answer 13

Lithium was superior to valproate; combination of lithium + valproate was best.

Question 14

What augmentation improves Valproate efficacy in mania?

Answer 14

Aripiprazole combined with valproate is superior to valproate alone.

Question 15

What is the plasma level threshold for Valproate efficacy in mania?

Answer 15

Levels >94 mg/L show strongest response; <55 mg/L similar to placebo.

Question 16

What are common dose-related side effects of Valproate?

Answer 16

Nausea, weight gain, tremor, sedation, hair loss, confusion, and hyperammonaemia.

Question 17

What is the effect of Valproate on tremor?

Answer 17

Dose-related intention/postural tremor in up to 25% of patients.

Question 18

What are serious hematologic and hepatic side effects of Valproate?

Answer 18

Thrombocytopenia, leucopenia, red cell hypoplasia, fulminant hepatic failure.

Question 19

What endocrine side effects can Valproate cause in women?

Answer 19

Hyperandrogenism, PCOS-like changes; teratogenicity risk in pregnancy.

Question 20

What cognitive risk does prenatal Valproate exposure carry?

Answer 20

Impaired cognitive development in children exposed in utero.

Question 21

What baseline tests are recommended before starting Valproate?

Answer 21

Full Blood Count (FBC), Liver Function Tests (LFTs), weight or BMI.

Question 22

What is the monitoring schedule for Valproate during treatment?

Answer 22

Repeat FBC and LFTs at 6 months; monitor weight/BMI.

Question 23

How should Valproate be discontinued?

Answer 23

Taper slowly over at least 1 month.

Question 24

Why is Valproate contraindicated in women of childbearing potential?

Answer 24

Due to its teratogenicity and risk of cognitive impairment in fetus.

Question 25

What precautions should be taken if Valproate is essential for women of childbearing age?

Answer 25

Use with specialist advice and prescribe prophylactic folate.

Question 26

How does aspirin affect Valproate levels?

Answer 26

Displaces valproate from protein binding and inhibits metabolism, increasing toxicity.

Question 27

Which drugs can increase Valproate levels via CYP inhibition?

Answer 27

Erythromycin, fluoxetine, cimetidine.

Question 28

Which drugs have increased plasma levels due to Valproate?

Answer 28

Lamotrigine, quetiapine, TCAs (esp. clomipramine), warfarin, phenobarbital.

Question 29

What effect does Valproate have on plasma olanzapine levels?

Answer 29

May significantly lower olanzapine levels (mechanism unknown).

Question 30

What should be monitored if LFTs are raised during Valproate therapy?

Answer 30

Albumin and clotting time.

Question 31

What dose-related adverse effects are commonly seen with Valproate?

Answer 31

Nausea, weight gain, tremor, sedation, hair loss (often regrows with altered texture), and hyperammonaemia.

Question 32

How common is tremor with Valproate and what type is it?

Answer 32

Up to 25% of patients may experience dose-related intention or postural tremor.

Question 33

What cognitive effect can Valproate have, especially when combined with other psychotropics?

Answer 33

Valproate may cause confusion or cognitive dulling, particularly when used with other sedatives or anticholinergics.

Question 34

What dermatological side effect is associated with Valproate and what can improve it?

Answer 34

Hair loss (alopecia), which often improves with time and may be managed with zinc supplementation.

Question 35

What endocrine side effects does Valproate cause in women?

Answer 35

Valproate can increase androgen levels in women, leading to acne and PCOS-like features, especially in those who are obese or have a family history of PCOS.

Question 36

What metabolic effects are associated with Valproate?

Answer 36

Weight gain, especially in women; Valproate is associated with greater weight gain than lithium or carbamazepine.

Question 37

What serious hepatic side effect is associated with Valproate?

Answer 37

Rarely, Valproate may cause fulminant hepatic failure.

Question 38

What hematologic side effects are associated with Valproate?

Answer 38

Valproate can cause thrombocytopenia, leucopenia, and red cell hypoplasia.

Question 39

What is hyperammonaemic encephalopathy in the context of Valproate use?

Answer 39

A serious condition caused by elevated ammonia levels; can occur with or without raised liver enzymes.

Question 40

Which patients are at increased risk of hyperammonaemic encephalopathy on Valproate?

Answer 40

Those with urea cycle disorders; should be screened for if suspected, especially in pediatric patients.

Question 41

What syndrome can occur when Valproate is used with lamotrigine?

Answer 41

Valproate can increase lamotrigine levels, raising the risk of Stevens-Johnson Syndrome (SJS).

Question 42

What are signs of hepatotoxicity that patients on Valproate should be educated about?

Answer 42

Jaundice, vomiting, fatigue, abdominal pain—patients should seek immediate medical help if these occur.

Question 43

What neurological side effect may occur due to Valproate’s effect on ammonia metabolism?

Answer 43

Encephalopathy, characterized by confusion, lethargy, and altered mental status.

Question 44

How can hair loss with Valproate be managed pharmacologically?

Answer 44

Zinc supplementation may help improve Valproate-induced hair loss.

Question 45

Why is Valproate especially risky for women of childbearing potential?

Answer 45

It is associated with teratogenicity and may cause neurodevelopmental disorders in children exposed in utero.

Question 46

What effect does Valproate have on the liver function tests (LFTs)?

Answer 46

Valproate can raise LFTs, and if elevated, albumin and clotting times should also be monitored.

Question 47

What should be the clinical approach if a patient develops elevated LFTs while on Valproate?

Answer 47

Monitor albumin and clotting time, and assess for signs of hepatic dysfunction.

Question 48

What endocrine axis is commonly affected in women taking Valproate?

Answer 48

The hypothalamic-pituitary-ovarian axis, potentially leading to hyperandrogenism and menstrual disturbances.

Question 49

How does Valproate affect reproductive hormones in women?

Answer 49

Increases testosterone levels, potentially leading to features of PCOS such as acne, hirsutism, and menstrual irregularity.