Hyperbolic dose reduction
Hyperbolic dose reduction
When PET imaging data was used to examine serotonin receptor occupancy at various doses of SSRIs, it was found that the relationship between dose and occupancy was not linear. Studies recommended that reducing SSRI doses “hyperbolically” would reduce the risk of discontinuation symptoms.
This hyperbolic style of dose reduction involves making smaller decreases in the dose towards the end of the withdrawal period and is often applied when reducing and stopping benzodiazepines.
This advice has been adopted by the latest NICE guidelines, due to be released imminently and will recommend reducing SSRI dosages proportionally rather than by a regular fixed amount or through a linear approach. As an example, the guidelines recommend reducing a dose in steps of 75 or 50 per cent of the previous dose, so it could take several weeks or even months to complete a full withdrawal.
The guidelines highlight that the speed and duration of withdrawal should be led by the person taking the medication, so the prescriber needs to have an open discussion with the individual and a joint decision made.
The NICE guidelines recommend continuing medications for at least six months after the remission of symptoms. The guidelines also emphasise the importance of the individual being monitored during the withdrawal period for any mood changes and discontinuation symptoms. The frequency of this monitoring will be decided dependent on clinical need.
The following case study involves an individual who had a successful antidepressant withdrawal using hyperbolic dose reductions.
Case study 2
Diana is a 45-year-old woman with a diagnosis of depression and lives alone. She has decided that she wants to stop taking her SSRI medication. As she trusts her local community pharmacist, she approaches her first.
Medication: Mirtazapine 30mg at night; Sertraline 100mg in the morning.
Diana wanted to speak to a female professional. During the conversation with her local community pharmacist, Diana said that she had often not been able reach an orgasm while on sertraline and wanted to stop taking it. Diana does not currently have a partner but sexuality is very important to her quality of life. Diana’s request is taken seriously and dealt with sensitively. Sertraline is well known to cause sexual dysfunction in more than 70 per cent of individuals.
Upon further exploration, it transpires that Diana skips one or two doses of sertraline every month in order to be able to achieve orgasm, then re-starts her sertraline again.
A plan was made with Diana, at a speed which was comfortable for her. The current evidence was discussed and the possible withdrawal effects explored, as well as what to do about them.
| Week 1 | Sertraline 100mg OM |
| Week 2 & 3 | Sertraline 50mg OM |
| Week 4-6 | Sertraline 25mg OM |
| Week 7 | STOP or if withdrawal effects, take 12.5mg |
The pharmacist asked Diana if she would like to try to stop the sertraline or replace it with something else. She was uncertain and slightly worried, so a joint decision was made to increase the mirtazapine dose to 45mg. If Diana’s depression returned or it wasn’t well controlled, she would be referred to the GP or the local mental health service. A list of emergency numbers (e.g. the Samaritans and other local services) was also provided.
Once Diana was happy with the plan, the pharmacist discussed it with the prescriber, who agreed with the course of action. As Diana was discontinuing only one antidepressant and remaining on mirtazapine, the speed of withdrawal of sertraline could be increased. She reduced the dose of sertraline successfully using the schedule shown above.
If Diana was discontinuing her only prescribed antidepressant, the withdrawal schedule would be extended over three to six months, using very small dosages in the last steps. However, Diana successfully discontinued her sertraline with no withdrawal effects and no relapse. Her quality of life has improved as she no longer experiences delayed, infrequent or absent orgasms.