Antidepressants

Treatment

• First choice - antidepressant with best-fit profile. In the absence of special factors consider fluoxetine or sertraline. Where there is a risk of overdose, SSRIs and mirtazapine are safest, venlafaxine is of intermediate risk and tricyclics are the most toxic.
• Counsel patient following the bullet points below in achieving the best use of medicines.
• Review at 1 to 2 weeks for side-effects.
• Review again at 4 to 6 weeks to check response. Consider an earlier review in the 18 to 30 year age group.  An adequate trial is a therapeutic dose for 4 weeks in adults and 6 weeks in older people.  For a partial response obtained after 4 or 6 weeks, continue for 2 more weeks in the adult population (3 in older people) in an effort to convert to a full response.
• If a full response is not obtained, check compliance, reassess clinical condition, consider increased dose where appropriate or change to a different class of antidepressant. See Antidepressant switching.
• After remission of symptoms, continue treatment at the dose the patient responded to for a minimum of 6 months in adults (1 year in older people) to reduce the risk of relapse by up to 50%.
• Consider maintenance treatment for patients with:  
  • 3 or more episodes in 5 years
  • more than 5 episodes
  • fewer episodes but with persistent risk factors present. 
• Gradually reduce and stop antidepressants to avoid discontinuation reactions. Aim to achieve this over a period of at least 4 weeks. Venlafaxine and paroxetine tend to be most problematic due to their short half-lives. Offer patient information leaflet ‘A handy fact sheet on coming off antidepressants’.

Achieving the best use of medicines

• Give positive advice regarding the benefits of treatment.
• Reinforce that antidepressants are not addictive.
• Inform patients about the potential side-effects.
• Inform patients about probable lack of initial benefit.
• Advise on timing of dosage.
• Advise that treatment is likely to be continued for at least 6 months (12 months in older people).
• Reinforce the importance of not discontinuing treatment too early.
• Reassure regarding the low risk of discontinuation reactions provided a planned gradual approach is taken.
• Be aware of increased risk of suicidal behaviour in patients under 25 years old particularly at the beginning of treatment or if the dose changes.

When switching between selective serotonin reuptake inhibitors (SSRIs), tricyclic (TCAs) and related antidepressants (see section 4.3), it is safer to reduce the dose of the first antidepressant and discontinue it before starting the second antidepressant. This is not always possible. Cross-tapering is an option for some switches but should always be done cautiously. Cross-tapering with mirtazapine is usually low risk.

Fluoxetine and paroxetine are inhibitors of cytochrome P450 isoenzymes; concomitant use with TCAs may result in a 2 to 3-fold increase in plasma levels of these TCAs.

Assess patients on an individual basis to determine how quickly the switch can be done, taking into account the following factors:

• urgency of the switch.
• the patient’s physical condition. Caution is required in older patients and those with co-morbidities.
• the potential for close monitoring.
• the risk that the switching regimen will confuse the patient and result in medication error.
• the risk of discontinuation reactions which can be unpleasant (see PIL)
  • higher risk with higher doses, longer duration of therapy (more than 6 weeks) and with antidepressants with a short half-life, eg venlafaxine and paroxetine.
  • lower risk with antidepressants with a long half-life, fluoxetine, and short duration of antidepressant therapy.
• the risk of serotonin syndrome which can be dangerous
  • serotonin syndrome is more likely to occur if the patient is on other drug therapy with serotonergic activity, for example triptans, tramadol, pethidine, selegiline, lithium and tricyclic antidepressants for neuropathic pain.

Switching antidepressants: use this table in conjunction with the previous notes

* Cross-tapering clomipramine with venlafaxine or a SSRI is not recommended.

^§  Fluoxetine at doses greater than 20mg may need to be withdrawn gradually rather than stopping abruptly.