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4.3 Antidepressant drugs

Mild depression
Antidepressants are not recommended for the initial treatment of mild depression, because the risk-benefit ratio is poor. However
where mild depression persists after other interventions, or is associated with psychosocial and medical problems, consider the
use of an antidepressant.
Moderate depression 
Offer antidepressant medication to all patients routinely, before psychological interventions.
Choice of drug
Discuss the choice of an antidepressant with the patient including side effect profile, discontinuation symptoms, any potential
interactions with other medication including herbal medicines and the individual perception of previous treatment and its effect.
When an antidepressant is to be prescribed in routine care it should be a generic SSRI because they are as effective as tricyclic
antidepressants and their use is less likely to be discontinued due to side effects. Fluoxetine or citalopram should be used first line
because they are generally associated with fewer discontinuation/withdrawal symptoms.
Changing therapy 
Treatment should be continued for a minimum of 4 weeks (6 weeks in the elderly) before considering that it is ineffective. If a
partial response has occurred reassess response after a further six weeks. If there is no response check compliance and consider
changing drug.
Duration of therapy 
Continue antidepressant therapy for at least 6 months after remission. For patients who have had two or more depressive
episodes in the recent past, and who have experienced significant functional impairment during the episodes, continue therapy
for two years.
Prescribing in older adults 
When prescribing in older adults the dose prescribed should be age appropriate taking into account the physical health and
concomitant medication. Side effects should be monitored closely when prescribing in older adults.
Augmentation of an Antidepressant Regime  
The following recommendations are made for augmentation of an antidepressant regime under a specialist mental health team:  

       ¤    The drugs that can be used to augment an antidepressant are lithium, an anti-psychotic such as aripiprazole, 
              olanzapine, quetiapine or risperidone, or another antidepressant such as mianserin or mirtazapine.
       ¤     Consideration must be given to the potential increase in side effects.
       ¤     When prescribing lithium the monitoring of lithium should be undertaken as per the Trust guidelines
       ¤     Patients prescribed anti-psychotics must be monitored for weight, lipids, glucose level and relevant side effects.
       ¤     The following drugs should not be used to augment and antidepressant regime: - buspirone, carbamazepine, lamotrigine, 
              valproate pindolol and thyroid hormones.
       ¤     Benzodiazepines should only be used concurrently with an antidepressant for a maximum of 2 weeks.


Consider offering: 
       ¤    Support and information
       ¤    Problem solving
       ¤    Benzodiazepines for 2-4 weeks maximum
       ¤    Sedative antihistamines e.g. hydroxyzine

Pharmacological Treatment  
      ¤    Before prescribing consider age, previous response to treatment, risk of deliberate self-Harm or accidental overdose,
            patient preference and cost effectiveness. 
      ¤    Offer an SSRI unless otherwise indicated (Paroxetine and escitalopram have a  license for GAD) 
      ¤    If one SSRI is not suitable or there is no improvement after 12 weeks then offer another SSRI.
      ¤    Minimise side effects by starting low and titrating slowly
      ¤    Long term treatment and doses at the upper end of the dose range may be  required
      ¤    Review efficacy and side effects after 2 weeks then at 4,6 and 12 weeks. 
      ¤    If treatment is long term then review at 8-12 week intervals.
      ¤    Follow SPCs for specific monitoring
      ¤    If improvement after 12 weeks then continue treatment for 6 months then slowly taper off over an extended period.
      ¤    If no improvement after 12 weeks then consider a different intervention OR  venlafaxine up to a maximum of 75mg.
            NB venlafaxine  is contra- indicated in patients with an identified very high risk of serious cardiac ventricular arrhythmia ,
            cardiac  ventricular arrhythmia ,  Venlafaxine should be used with caution in patients with established cardiac disease
            that may increase the risk of ventricular arrhythmias (e.g. recent myocardial infarction). Regular measurement of
            blood pressure is recommended for patients receiving venlafaxine.  
     ¤     If no improvement after two interventions review and if appropriate offer referral to specialist mental health service.
 Pregabalin - AMBER - initiation by LSCFT specialist clinician [Position Statement] 
 Prescribing of Pregabalin in primary care for the treatment of Generalised Anxiety Disorder can be continued provided that the
 treatment is initiated by a specialist and that certain prior criteria have been met. See Position Statement

                Click here for The Joint Formulary for psychotropic Medication (LCFT)


      ¤   Offer an SSRI licensed for panic disorder, unless otherwise indicated  (citalopram, paroxetine and escitalopram)  
      ¤   If SSRI not suitable or no response after 12 weeks consider clomipramine or  imipramine   
      ¤   Benzodiazepines, sedating antihistamines and antipsychotics should NOT be prescribed for panic disorder
      ¤   Review efficacy and side effects after 2 weeks then at 4, 6 and 12 weeks.   
      ¤   Long term treatment and doses at the upper end of the dose range may be required.
      ¤   If treatment is long term then review at 8-12 week intervals.
      ¤   Follow SPCs for specific monitoring
      ¤   If no improvement after two interventions review and if appropriate offer referral to specialist mental health services.
      ¤   The evidence for buspirone is equivocal and its use is NOT recommended by NICE.
      ¤   Buspirone should not be used in patients with epilepsy, severe renal impairment  (defined as creatinine clearance of 20 
           ml/minute or below, or a plasma creatinine above 200 micromoles/litre) or in patients with severe hepatic disease.
      ¤   Buspirone is licensed for short term use. Any patients initiated on buspirone by specialist mental health services and
           discharged to primary care should have buspirone stopped after two months of treatment, unless otherwise specified.
           Information from the manufacturer of buspirone indicates patients aren’t likely to  suffer from withdrawal after stopping 
Stopping or reducing antidepressants
All patients prescribed antidepressants should be informed that, although the drugs are not associated with tolerance or craving,
discontinuation symptoms may occur on stopping, missing doses or, occasionally, on reducing the dose of the drug. These 
symptoms are usually mild and self-limiting (in which case monitor and reassure) but occasionally can be severe. Cessation of
therapy should be managed over a minimum of 4 weeks.

4.3.1 Tricyclic and related antidepressant drugs

Tricyclics should be used only where SSRIs have proved ineffective. Care should be taken with their use because of potential 
cardiotoxicity and also toxicity in overdose. Lofepramine is an appropriate first choice. In the elderly, start with low dose and 
increase cautiously.
GREEN       Amitriptyline 
                    tablets 10mg, 25mg, 50mg     
                    liquid 25mg/5mL     
GREEN       Clomipramine capsules 10mg, 25mg, 50mg   
AMBER       Doxepin capsules 25mg, 50mg 
Less sedative 
GREEN       Imipramine - (nocturnal enuresis ONLY) 
                    tablets 10mg, 25mg 
                    syrup 25mg/5mL   
AMBER       Imipramine  - for use by LSCFT in exceptional circumstances only
BLACK         Imipramine is not recommended for use in depression or neuropathic pain in primary care 
GREEN       Lofepramine 
                    tablets 70mg suspension 70mg/5mL 
Dosulepin (dothiepin) is not recommended by NICE due to its association with ischaemic heart disease, cardiac arrhythmias
and fatalities following overdose
Trazodone is licensed for use in depressive illness, particularly where sedation is required. It is related to the tricyclic anti-
GREEN             Trazodone 
                         capsules 50mg, 100mg
                         tablets 150mg
GREEN            Trazodone oral solution SF 50mg/5mL [For titration/dose reduction  and patients with swallowing difficulties]
restricted use

4.3.3 Selective serotonin re-uptake inhibitors (SSRI)

SSRIs selectively inhibit reuptake of serotonin. NICE recommend that the initial choice of antidepressant should be an SSRI that is 
available as a generic drug (currently citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline). Locally fluoxetine, citalopram
and sertraline are primarily recommended as first and second line choices.
Fluoxetine has a higher propensity for drug interactions although it is less likely to cause a withdrawal reaction. Fluoxetine has
shown to have a favourable balance of risks and benefits for the treatment of depressive illness in under 18's. Citalopram is an
alternative first line SSRI which may be better tolerated and has fewer drug interactions than most other SSRIs. Sertraline is the
SSRI of choice in ischaemic heart disease.
Consider that fluoxetine, fluvoxamine and paroxetine have a higher propensity for drug interactions. Paroxetine is associated with 
a higher risk of discontinuation symptoms. However, all SSRIs can precipitate such withdrawal symptoms - consult the BNF for
tailoring of dose recommendations, do not stop treatment abruptly. 
First & Second Line 
GREEN            Fluoxetine 
                        capsules 20mg  
                        dispersible tablets 20mg   (for patients unable to swallow standard capsules)
                        liquid 20mg/5mL
GREEN           Citalopram tablets 10mg, 20mg    
GREEN           Sertraline tablets 50mg, 100mg  
Escitalopram: Major Depressive Illness
Escitalopram should be reserved for patients with major depressive illness only [As per product license]
GREEN            Escitalopram tablets 5mg, 10mg, 20mg 
restricted use            
MHRA Drug Safety Update - Citalopram and escitalopram: QT interval prolongation
Alternatives - see notes above 
GREEN             Paroxetine tablets 20mg, 30mg      
Escitalopram in generalised anxiety disorder  
See notes on generalised anxiety disorder above. 
GREEN              Escitalopram tablets 5mg, 10mg, 20mg 
Daily selective serotonin re-uptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE) 
Daily SSRI's may be used as an option to treat acquired PE but only after psychotherapy and management of the causative 
problem have failed to resolve the issue.
Patients should be referred to the psycho-sexual service in order to determine if a daily SSRI would be an appropriate treatment
AMBER            Daily SSRIs for the treatment of PE

4.3.4 Other antidepressant drugs

Third line only 
Mirtazapine can very rarley cause blood disorders - Patients should be advised to report any fever, sore throat, stomatitis or other 
signs of infection during treatment. Blood count should be performed and the drug stopped immediatley if blood dyscrasia
suspected. Can also increase appetite and weight gain, and cause anti-cholinergic side effects such as dry mouth and postural 
hypotension. Nausea, vomiting, dizziness, agitation, anxiety, and headache are most common features of withdrawal if treatment 
stopped abruptly or if dose reduced markedly; dose should be reduced over several weeks.
GREEN           Mirtazapine 
                        tablets 15mg, 30mg, 45mg
                        orodispersable tablets 15mg, 30mg, 45mg  (only for those with swallowing difficulties)
Take into account the toxicity in overdose for people at serious risk of suicide and be aware that venlafaxine is associated with a
greater risk of death in overdose.
When prescribing antidepressants other than an SSRI take into account the increased likelihood of the patient stopping treatment
because of side effects and the need to increase the dose gradually with venlafaxine, duloxetine and tricyclic antidepressants.
Treatment with venlafaxine should be initiated under specialist supervision/recommendation when used at 300mg/day or above. It
is contra-indicated in patients with an identified very high risk of serious cardiac ventricular arrythmia (e.g. those with a significant 
left ventricular dysfunction, NYHA Class III/IV), or those with uncontrolled hypertension. Venlafaxine should be used with caution in
patients with established cardiac disease that may increase the risk of ventricular arrhythmias (e.g. recent myocardial infarction). 
Regular measurement of blood pressure is recommeded for patients receiving venlafaxine.
GREEN         Venlafaxine
                      tablets/capsules m/r 75mg, 150mg, 225mg, 300mg, 375mg  
                      tablets 37.5mg, 75mg 
Vortioxetine is recommended as an option for the treatment of major depression episodes in adults by NICE TA367   
Where the condition has responded inadequately to 2 antidepressants within the current episode. 
GREEN             Vortioxetine (Brintellix®
                          tablets 5mg, 10mg, 20mg
Duloxetine for depression - prescribe by brand name only 
When prescribing antidepressants other than an SSRI take into account the increased likelihood of the patient stopping treatment
because of side effects and the need to increase the dose gradually venlafaxine, duloxetine and tricyclic antidepressants. Consider
the specific cautions, contra-indications and monitoring requirements for duloxetine. Regular measurement of blood pressure is
recommended for patients receiving duloxetine.
AMBER            Duloxetine (Cymbalta®) capsules 30mg, 60mg     
For initiation by a consultant psychiatrist only, in treatment resistant depression.  Please see shared care guideline here
SHARED CARE    L-Tryptophan tablets 500mg 
Other specialists interventions initiated by specialist mental health teams only:  
MAOIs phenelzine - AMBER with ongoing specialist review 
Antidepressants with lithium augmentation - AMBER with ongoing specialist review
Other antidepressants which may be initiated by LCFT are as follows: 
AMBER                Mianserin
(LCFT)                  tablets 10mg, 30mg
AMBER                Moclobemide 
(LCFT)                  tablets 150mg, 300mg
AMBER                Reboxetine 
(LCFT)                  tablets 4mg
Treatment of diabetic neuropathic pain with duloxetine - prescribe by brand name only. 
Duloxetine is to be prescribed for diabetic neuropathic pain when the use of tricyclic antidepressants are inappropriate, not
tolerated or ineffective.  Withdraw other antidepressants before initiating duloxetine.  Prescribe by brand name only. Treatment
should be reviewed after two weeks to assess tolerability, and then after two months to assess response – additional response
after this time is unlikely. 
GREEN                Duloxetine (Cymbalta®) capsules 30mg, 60mg 
Agomelatine (BLACK traffic Light)
Agomelatine should only be initiated and prescribing continued by a consultant psychiatrist from Lancashire Care Trust, for those
patients who had tried other antidepressant treatments, including where possible the NICE recommended options for the
management of treatment refractory depression. GPs should not be asked to pick up prescribing of agomelatine. All requests
should be directed through the Pharmacy Dept of Lancashire Care Foundation Trust initially for authorisation. Patients must be
monitored for symptoms suggesting hepatic dysfunction. Liver function tests must be performed in all patients: at initiation of
treatment, and then after six weeks, twelve weeks and twenty four weeks. Thereafter liver function tests should be checked
when clinically indicated.
Click here for the Joint Formulary for Psychotropic Medication LCFT.

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