Stop venlafaxine and start risperidone
Management of mania/hypomania in patients taking antidepressants: consider stopping the antidepressant and start antipsychotic therapy
The correct answer is stop venlafaxine and start risperidone. This man has developed mania, with elevated mood, overactivity, lack of sleep, pressured speech, risk-taking behaviour, extravagance, irritability, and grandiose and possibly paranoid delusions. The presence of delusions and the duration of >1 week help to differentiate this from hypomania.
Antidepressants are known to trigger mania or hypomania as a side effect when used alone in unipolar or bipolar depression. This is also sometimes termed a manic ‘switch’ ie from depression to mania. The risk seems higher with SSRIs and tricyclic antidepressants (TCAs) and particularly high with venlafaxine. There is some evidence that this risk is lower with mirtazapine, however, cases have been reported as well.
Cessation of antidepressant treatment is recommended when patients with depression develop mania. NICE guidance on the management of bipolar disorder advises:
‘If a person develops mania or hypomania and is taking an antidepressant (as defined by the BNF) as monotherapy:
Consider stopping the antidepressant and
Offer an antipsychotic regardless of whether the antidepressant is stopped.’
NICE guidance then recommends that the choice of antipsychotic should be one of:
Haloperidol
Olanzapine
Quetiapine
Risperidone
If one of these antipsychotics fails at the maximum tolerated dose or is not tolerated, then an alternative from the same list should be tried next. If these fail, the addition of lithium is the third line, and sodium valproate is the fourth line.
Cross-taper the patient back to sertraline is not correct. Sertraline and other SSRIs are not indicated in the treatment of acute mania and may worsen it. They may have a lower risk of inducing mania than venlafaxine, however, all antidepressants are recommended to be stopped by NICE during an acute manic episode for patients, regardless of whether they are on antipsychotic therapy. NICE also recommends fluoxetine as the SSRI of choice in combination with olanzapine in treating a depressive episode in patients with bipolar disorder. Fluoxetine has a very long half-life of 4-6 days, which can limit extreme mood variations that can trigger mania. An alternative antidepressant in bipolar disorder would be quetiapine monotherapy. A third line is lamotrigine monotherapy, however, this is known to also trigger mania and should be up titrated very slowly.
Cross-taper the patient to mirtazapine and add sodium valproate modified-release is not correct. There is some evidence that hypnotic antidepressants like mirtazapine may be less likely to induce mania, however, in this scenario, the man has developed acute mania which would need to be treated first. Aripiprazole is a relatively novel atypical antipsychotic that has a favourable side-effect profile in comparison to other conventional antipsychotics. This relates to its partial agonism (as opposed to antagonism) of the D2 dopamine receptor. However, it is not recommended by NICE as a first-line antipsychotic for the management of acute mania in adults (see list above) but is recommended first-line in the management of mania in children and adolescents.
Sodium valproate modified-release is a second-line mood stabiliser, after lithium. In the treatment of acute mania, NICE recommends antipsychotics as first-line, with a different antipsychotic to the first as second-line if the first is not effective. These would need to be titrated to the maximum BNF dose. In case this is ineffective, the addition of lithium would be the third line, and if lithium is ineffective, contraindicated or not suitable, valproate could then be considered (fourth line). This should be avoided in women of childbearing age due to its high teratogenic potential, unless necessary and where a pregnancy prevention programme is in place.
Prescribe two-week course of oral clonazepam is not correct. While this may help control the manifestations of mania, it does not address the cause which is likely venlafaxine. Benzodiazepine use also carries a risk of overdose, and although an isolated benzodiazepine overdose has a low lethal potential, a mixed overdose with other CNS and respiratory depressants, for example, alcohol, over the counter (OTC) co-codamol or OTC promethazine could be lethal. This patient also has a high risk due to his previous suicide attempt and it would therefore be a really bad idea to prescribe these in the community, without the level of monitoring available through inpatient or outpatient secondary care teams.
Start lithium is not correct. Lithium is very effective in manic and depressive relapse prevention in bipolar disorder but it is not recommended as 1st line for the management of acute mania in patients who are not already on antipsychotics. The reason for this is it has a much slower onset of action of around 1-2 weeks, as opposed to antipsychotics which have a rapid onset. Furthermore, NICE advises considering stopping the antidepressant:
‘If a person develops mania or hypomania and is taking an antidepressant (as defined by the BNF) in combination with a mood stabiliser, consider stopping the antidepressant.’
