Q: If a patient does not respond to an adequate dose of an antidepressant, what is the best regimen for switching to a drug in a different class?
There are possible pharmacokinetic and pharmocodynamic interactions that can occur which differ between drugs. Any risk must be balanced against the need to avoid undue delay, and cross tapering can usually be safely done.
However, it is important to be aware of the potential interactions, and if in doubt, check in the BNF, MIMS or the manufacturer's recommendations.
When changing from a tricyclic antidepressant to an SSRI, the key point to remember is that some SSRIs interfere with tricyclic metabolism and may increase plasma concentrations.
Fluoxetine and paroxetine have this effect, but sertraline and citalopram/escitalopram have minimal effect.
If cross tapering is done, I suggest reducing the dose of the tricyclic before starting the SSRI.
The dose of tricyclic can be reduced to 100mg before starting citalopram/escitalopram or sertraline, and to 50mg for the others. Finally, taper off the tricyclic over a week or so.
When switching from an SSRI to a tricyclic, you can start the tricyclic straight away. Taper off the SSRI over a week, while increasing the tricyclic dose. Fluoxetine should be stopped, but the dose of the tricyclic should be increased slowly, remembering that the effective half-life of fluoxetine is a week.
If you are switching a patient from an SSRI to venlafaxine or duloxetine, the cross taper can be more rapid.
If switching to mirtazapine, it can be started immediately at a dose of 15mg and then increased as the SSRI is tapered over one to two weeks.
For other antidepressants, the regimen depends on the pharmacology. It is important to avoid the interaction of an SSRI with a monoamine oxidase inhibitor (MAOI). Stop the patient's SSRI, venlafaxine or clomipramine for one to two weeks before starting an MAOI or moclobemide. The gap should be five weeks for fluoxetine. If switching in the other direction, leave a two-week gap, unless switching from moclobemide, where 24 hours is enough.
A good source of information is the Bethlem and Maudsley Prescribing Guidelines.
The British Association for Psychopharmacology guidelines (www.bap.org.uk) advise on treating depression.
- Dr Ian Anderson, senior lecturer and honorary consultant psychiatrist, University of Manchester, Manchester Royal Infirmary
Q: Should all patients with diabetes or cardiovascular disease (CVD) take ACE inhibitors, irrespective of whether they have left ventricular dysfunction or proteinurea, and even if they do not have hypertension or heart failure?
Taking diabetes first, the question is whether blocking the renin-angiotensin system is appropriate in all diabetics.
Two major trials have looked at this.
The HOPE study compared the use of ACE inhibitors versus placebo on cardiovascular events in patients with diabetes (J Renin Angiotensin Aldosterone Syst 2000 1(1): 18-20). The LIFE study compared an angiotensin II receptor blocker-based antihypertensive regimen with one based on atenolol (J Am Coll Cardiol 2005 46: 770-5).
In both studies, blocking the renin-angiotensin system brought benefits, despite similar (but not identical) reductions in BP.
However, this does not mean that all diabetic patients should receive an ACE inhibitor or angiotensin II receptor blocker because the studies focused on high-risk patients.
In the HOPE study, all patients were older than 55 years and had at least one other risk factor such as known vascular disease, cigarette smoking or high cholesterol.
In the LIFE study, patients were all hypertensive with ECG evidence of left ventricular (LV) hypertrophy.
The diagnosis of diabetes alone is not a reason for prescribing drugs to block the renin-angiotensin system.
As for patients with CVD, but without diabetes, heart failure or hypertension, the HOPE study suggests we should consider the use of ACE inhibitors (and presumably angiotensin II receptor blockers) in patients who are given prophylaxis with aspirin.
However, the PEACE study from 2004 showed no benefit of ACE-inhibitor in patients with stable coronary heart disease and preserved LV function who were receiving standard therapy (N Engl J Med 2004 351: 2,058-68).
The difference between the two studies reflects the more frequent use of statins in the PEACE trial leading to low event rates.
- Dr Steve Bain, professor of medicine (diabetes), University of Wales, Swansea.