Antidepressants

To consider the management of depression and anxiety disorders, the use of non-pharmacological treatments and appropriate use of antidepressants including timely review and deprescribing.

Essential medicines:

for some people who have experienced severe and/or enduring mental illness. Such severe mental illness can be recurrent, debilitating, and potentially lethal.

Non-essential medicines:

for the treatment of mild depression and/or anxiety, neuropathic pain associated with diabetes and other conditions.

Before starting antidepressant treatment, discuss with the individual, ensuring a person-centred approach with the individual:^25,105,224

• the use of non-pharmacological treatment options first (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027)
• if pharmacological treatment is to be used prescribers should:
  • consider the benefits and risks of treatment taking into account the individual’s existing medications and comorbidities and the evidence base.
  • inform the individual of the discontinuation/withdrawal effects of antidepressants
  • discuss the different adverse effect profiles of antidepressants and consider the positive and negative effects they would find beneficial or like to avoid
  • discuss the likely response time to antidepressant treatment e.g. some show effect within one to two weeks for depression and set clear therapeutic goals
  • discuss when treatment may need to be stopped

Depressive illness^{105,133,180,224,225,226}

Mild depressive illness

The risk–benefit ratio is poor for mild depression, therefore consider non-pharmacological options (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027).¹⁰⁵

A trial of antidepressant treatment may be appropriate for people with

• a history of moderate or severe depression
• initial presentation of sub-threshold depressive symptoms existing over a long period (typically at least two years)
• sub-threshold depressive symptoms or mild depression that persists after other interventions.

Moderate to severe depressive illness

The use of antidepressants in combination with psychological therapies e.g. cognitive behavioural therapy (CBT) is more effective, with lower discontinuation rates, than treatment with antidepressants alone. (See NHS inform for CBT resources.)

Monitor efficacy and individual’s response, and if:

• no response to antidepressant at two to four weeks (citalopram, fluoxetine, paroxetine 20mg/day, escitalopram 10mg/day, sertraline 50mg/day, mirtazapine 30mg/day)
  • review diagnosis
  • check adherence with antidepressant dose and frequency
  • consider changing to another selective serotonin re-uptake inhibitor (SSRI) or other antidepressant, and review in two to four weeks
• partial response at four weeks:
  • consider revisiting/discussing the addition of non-pharmacological treatments (e.g. physical activity, CBT)
  • for mirtazapine, serotonin and norepinephrine reuptake inhibitors (SNRIs) or lofepramine consider increasing dose, if tolerated
  • SSRIs demonstrate a flat dose-response effect for efficacy (citalopram, fluoxetine, paroxetine 20mg/day, escitalopram 10mg/day, sertraline 50mg/day). If no significant improvement it may be more appropriate to change the antidepressant rather than increase the dose

Chronic or recurring depression

For people who are at significant risk of relapse or have a history of recurrent depression, discuss treatments to reduce the risk of recurrence, such as continuing medication, augmentation of medication (e.g. initiation by a specialist psychiatric prescriber of an antipsychotic or lithium therapy - see Quality prescribing for antidepressants for more details) or psychological treatment (e.g. CBT). Treatment choice should be influenced by:

• previous treatment history, response to previous treatment and any discontinuation symptoms including the consequences of a relapse
• residual symptoms
• the individual’s preference

Depression in dementia

Non-pharmacological management of symptoms of stress and distress in dementia should be considered and implemented as first line approaches.

Antidepressants demonstrate limited benefits in treating depression in people with dementia. For some individuals, however, they may reduce depressive symptoms and improve general functioning. Sertraline, citalopram and trazodone have been used and are associated with modest reductions in symptoms of stress and distress in dementia.

Anxiety disorders: generalised anxiety disorder, panic disorder and obsessive compulsive disorders^{180,215,225,227,228}

Mild anxiety disorders

Consider non-pharmacological options as the effectiveness of antidepressants in mild anxiety disorders is uncertain (see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027).¹⁰⁵

Moderate to severe anxiety disorders

Antidepressants have been shown to be effective in the treatment of a range of moderate to severe anxiety disorders.

SSRIs and SNRIs are used, with SSRIs as first line pharmacological agents, due to their efficacy and safety profile, in the treatment of generalised anxiety disorders (GAD), panic disorders and obsessive-compulsive disorder (OCD). Tricyclic antidepressants can be effective in some anxiety disorders, but their use is limited due to the side-effect profile. Propranolol is not recommended for use in anxiety disorders by NICE. There is significant risk of harm in overdose - see Health Services Safety Investigations Body advice.

When used to treat generalised anxiety disorder (GAD), SSRIs, venlafaxine and duloxetine should initially be prescribed at half the normal starting dose and titrated to the normal antidepressant dosage range as tolerated (initial worsening of anxiety may be seen when treatment is started).²²⁹

Monitor efficacy and response to treatment, if:

• no response to treatment consider:
  • in OCD increasing the antidepressant dose or offer an alternative antidepressant from a different class
  • in GAD offer high intensity psychological intervention or an alternative antidepressant from a different class
• partial response to treatment:
  • in GAD offer a high intensity psychological intervention in addition to their antidepressant
  • in OCD offer CBT in addition to an antidepressant

Antidepressants should not be stopped abruptly especially in individuals with:

• previous discontinuation/withdrawal symptoms e.g. flu-like symptoms, electric shocks (brain zaps), vivid dreams, dizziness or diarrhoea - slow managed reduction may be more appropriate
• history of severe and enduring illness – suddenly stopping treatment may lead to a deterioration in mental stability and/or withdrawal effects. Planned medicines reduction should be agreed between the individual and their prescriber
• support from secondary care psychiatry teams should be considered for complex cases or severe discontinuation/withdrawal symptoms.

Antidepressants:²¹⁵

• are associated with hyponatraemia, particularly in older people. Consider in all individuals who develop drowsiness, confusion or convulsions
• are associated with an increased falls risk in older people
• tricyclic antidepressants, high dose citalopram and high dose escitalopram can prolong QTc especially when combined with other medicines that affect cardiac rhythm

Discontinuation or withdrawal effects:

• paroxetine or venlafaxine are more commonly associated with discontinuation or withdrawal effects, especially when stopped suddenly
• some individuals may be more sensitive to discontinuation or withdrawal effects than others
• those people receiving higher doses and/or longer-term treatment may require slower reductions

SSRIs:^215,227

• increased risk of gastrointestinal (GI) bleeds, especially for older adults and those receiving medicines associated with GI bleeds (anti-inflammatory, antiplatelets and anticoagulants). Consider GI protection
• restlessness can occur when starting/increasing SSRI doses and usually settles within the first 10 days
• can contribute to thoughts of suicidal/self-harm for a small minority of individuals with under 30 years olds being at greater risk

Reducing or stopping antidepressants should done gradually and be considered when:¹⁰⁵

• treatment is ineffective
• therapeutic goals have not been achieved and an alternative approach is required
• treatment course is complete e.g.
  • first episode of moderate to severe depression - after six-month course
  • anxiety – after 12-month course
• adverse effects are present, for example:
  • if significant or severe agitation/restlessness (akathisia) develops, although very rare

Antidepressants should be reviewed regularly, especially in long-term use (≥2 years), to assess ongoing need, effectiveness, and potential for deprescribing.

When stopping antidepressant medicines consider:^180,224

• individual’s preferences, needs and experience of withdrawing antidepressant medication if applicable
• urgency of withdrawal e.g. significant adverse effects may require stopping quickly
• half-life and duration of treatment. Those with a short half-life (e.g. paroxetine/venlafaxine) may need to be tapered more slowly and require more reduction steps
• severity of the discontinuation/withdrawal symptoms. If severe consider:
  • reinstating the previous antidepressant dose
  • re-attempting dose reduction after symptoms have resolved
  • reducing at slower rate with smaller reductions

For further detailed information on deprescribing antidepressants, see Quality prescribing for antidepressants: a guide for improvement 2024 to 2027 under “reducing and stopping antidepressants”.¹⁰⁵

Supporting people who do not or cannot reduce/stop

For some individuals it may not be appropriate to stop when:

• they have not completed the course of treatment
• longer term treatment may be required due to:
  • repeated depressive episodes
  • generalised anxiety disorder with repeated relapse
  • neuropathic pain
  • where the continuing treatment in the medium term may be appropriate due to individual circumstances, e.g. recent stress/bereavement

If stopping treatment is not feasible consider the range of options for reducing as outlined in Quality prescribing for antidepressants: guide for improvement 2024 to 2027.¹⁰⁵

Specific areas/situations where medication may need to be introduced or increased

Antidepressant medication may need to be reintroduced or increased when:

• individuals experience recurrence or discontinuation/withdrawal symptoms. The previous lowest tolerated dose should be prescribed
• therapeutic goals are not achieved

Does the person understand the outcomes of the review, including risks and benefits?

• Discuss reducing/stopping treatment in a supportive environment (including concerns of relapse)

Is drug therapy tailored to the individual?

• When supporting the individual through the reduction process, reassure them that discontinuation/withdrawal symptoms:
  • should gradually improve for most people, but some may experience longer term effects
  • are being monitored. If symptoms are severe, consider reinstating their previous antidepressant dose and frequency of administration
  • are not a relapse of their depression and/or anxiety (as relapse does not usually occur within one to two weeks of stopping an antidepressant)

Agree the plan

• Agree the dose change (share a written and/or verbal plan)
• Discuss non-pharmacological options
• Give information on self-monitoring and what to do if symptoms re-occur
• Continue regular review, whether treatment changing or remaining the same
  • individual circumstances have not changed, e.g. treatment course complete and therefore the individual may be ready to stop
  • therapeutic aims still being met, e.g. no deterioration in symptoms
  • there is no medication-related harm requiring a change/reduction in treatment

• self-management/support tools
• decision aids

Get help with your mental health and wellbeing on NHS inform (includes links to SilverCloud® (mental wellbeing courses), Daylight® (digital CBT), Sleepio® (digital CBT))

Information on stopping antidepressants on the Royal College of Psychiatrists website

Choice and Medication available via NHS inform

National Therapeutic Indicators (NTIs) use prescription data in specific areas to provide a measure of prescribing activity for comparison across NHS Boards, Health and Social Care Partnerships (HSCPs), GP clusters and GP practices.

NTIs are available to view online.

NTIs benchmark prescribing across set parameters and are presented in a variety of ways. Examining variation over time can indicate where improvements in prescribing can be made. The indicator detail provides further information and suggested actions.

Indicators for this hot topic include:

• Adults prescribed antidepressant medications long-term (equal to or more than 2 years) as a proportion of adults in receipt of antidepressant medications. See the chart below.
• People receiving three or more of benzodiazepine/z-drug, opioid (including tramadol), gabapentinoid, antidepressant or antipsychotic (excluding depots) (CNS triple whammy)
• Mental health (GI bleed): number of people prescribed SSRI plus another medication known to increase risk of GI bleed without gastro-protection
• Mental health (long-term benzodiazepine (BZ) with antidepressant): Number of people prescribed benzodiazepine or z-drug (for more than eight weeks) with an antidepressant

Adults prescribed antidepressant medications long-term (equal to or more than 2 years) as a proportion of adults in receipt of antidepressant medications

(Click on image to enlarge)