3 Clinical psychopharmacology3.4 Therapeutics
3.4.2.1 Dose ranges, minimum effective doses and time scales
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Written by Resident Doctor Committee · Published
Dose terminology
Term | Meaning |
|---|---|
Starting dose | First dose, chosen for tolerability; it may already be therapeutic |
Minimum effective dose | Lowest dose with shown benefit for the indication |
Maximum recommended dose | A product-specific ceiling, not a target |
High-dose antipsychotic treatment exceeds one drug's maximum or a combined 100% of individual maxima, and needs specialist justification and ECG monitoring.
Above the therapeutic plateau, higher doses add more adverse effects than benefit.
Minimum effective antidepressant doses
These are daily doses in adult depression, from the Maudsley Prescribing Guidelines.
Antidepressant | Minimum effective dose | Notes |
|---|---|---|
Sertraline | 50 mg | Also the usual starting dose |
Citalopram | 20 mg | |
Escitalopram | 10 mg | Half the dose of racemic citalopram; maximum 20 mg |
Fluoxetine, paroxetine | 20 mg | |
Trazodone | 150 mg | |
Venlafaxine | 75 mg | Noradrenergic action becomes appreciable from about 150 mg |
Duloxetine | 60 mg | |
Mirtazapine | 30 mg | Not the 15 mg starting dose; maximum 45 mg |
Moclobemide | 300 mg | Reversible inhibitor of monoamine oxidase A; 300 mg is also the starting dose; up to 600 mg |
Lofepramine | 140 mg | Usually 70 mg twice a day; up to 210 mg |
Amitriptyline, imipramine | Often 75 to 100 mg |
Before calling depression treatment-resistant, confirm the person took a tolerated therapeutic dose for long enough.
Half-life and steady state
Steady state takes four to five half-lives, so repeated dose increases before then can cause delayed toxicity.
A long half-life buffers missed doses but prolongs accumulation and adverse effects.
Drug | Elimination half-life | Consequence |
|---|---|---|
Aripiprazole | About 75 hours, the longest of the common oral antipsychotics | About two weeks to steady state |
Olanzapine | Mean about 30 hours (range 21 to 54) | Once daily; steady state in about a week |
Risperidone | About 20 hours for the active moiety | Once or twice daily |
Amisulpride | About 12 hours, with no modified-release form | Low doses once daily; higher doses split into two |
Clozapine | About 12 hours, variable | Often divided, with a larger evening dose |
Quetiapine immediate-release | About 6 hours | Often twice daily |
Diazepam has the longest half-life of the commonly prescribed benzodiazepines, extended by its long-lived active metabolite desmethyldiazepam, especially in older people.
Depots and modified-release formulations
Zuclopenthixol decanoate 200 mg every 2 weeks (400 mg every 4 weeks) corresponds to about 50 mg haloperidol decanoate every 4 weeks.
Loading, oral overlap and conversion differ between long-acting injections, so each follows its own product instructions.
Methylphenidate is prescribed by brand, because the immediate to modified-release split decides how much drug is active late in the day.
Methylphenidate product | Immediate to modified-release split | Duration |
|---|---|---|
Concerta XL and its generics | 22:78 | About 12 hours, leaving the most drug in the evening |
Modified-release capsules, such as Medikinet XL | 30:70 or 50:50 | About 8 hours |
Immediate-release tablets | All immediate | 3 to 4 hours |
Time to clinical effect
Sedation and hypotension appear within hours, and agitation may improve over hours to days.
Core antipsychotic benefit develops over weeks and is commonly assessed at four to six weeks.
Because sedation comes before antipsychotic benefit, prescribers should not raise the dose for persistent early agitation alone.
Antidepressant benefit needs several weeks to assess, and obsessive-compulsive disorder often needs longer.
Hypnotic and stimulant effects can appear with the first dose.