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Choosing an antidepressant - quick tips, dosages, side effects

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Antidepressant (AD) Advantages Disadvantages

Citalopram and

Sertraline 

 

SSRI

Firstline

Reduced risk of toxicity in overdose

Better tolerated than other ADs; better compliance

Fewer interactions; due to shorter half lives; better in those on multiple medications

Effective in the treatment of depression with anxiety

Increased risk of bleeding; consider a PPI in older people and in patients on NSAIDs or aspirin

SSRIs can exacerbate hyponatraemia; especially in the elderly

Citalopram and escitalopram increase the QT interval - avoid with these drugs

Sertraline may result in higher rates of diarrhea

Augmnetned by mirtazipine 

 

Fluoxetine and Paroxetine

SSRI

Fluoxetine is more commonly used in younger adults; start with 10mg daily for several days

Fluoxetine; lower rates of withdrawal symptoms and suicidal thoughts or behavior 

Paroxetine can be used for pain treatment in patients with depression

High propensity for interactions

Increased likelihood of the person stopping treatment because of side effects

Monitor the elderly more closely for side-effects and start on low dose

Paroxetine; higher rate of withdrawal symptoms such as suicide, higher risk of weight gain an sexual symptoms

Fluoxetine; longer half life and more potential interactions

Avoid in women on tamoxifen

Venlafaxine 

Second line medication if SSRIs have failed

low risk of weight gain

Few interactions

Few side effects

Enhanced efficacy that extends over the entire spectrum of major depression and anxiety disorders; SNRIs may be more effective than SSRIs in resistant or refractory (difficult-to-treat) depression

Increase doses gradually to avoid side effects

Dangerous in overdose

Nausea and vomiting  typically subsides within one week

May increase blood pressure

Duloxetine

SNRI

Used in chronic pain (fibromyalgia, chronic musculoskeletal pain, peripheral neuropathy) as well as depression

Increased likelihood of stopping treatment because of side effects; need to increase the dose more gradually

May increase blood pressure

Vortioxetine 

Serotonin modulator

Less or no effects on sexual dysfunction

no weight gain

safe in renal and hepatic impairment

relatively long half-life, vortioxetine presents a low risk of discontinuation symptoms 

Not usually initiated in primary care - check your local CCG guidelines 

linked with high rates of nausea (typically highest in the first week of treatment). However, in studies, it had no significant effect on body weight in either short-term or longer-term (6 month) research trials accessing weight gain. 

Trazodone

Serotonin modulator

Causes drowsiness, may hep with sleep problems 

May rarely be associated with priapism, a painful and long-lasting erection considered a medical emergency

Mirtazipine

Atypical antidepressants

Can help with sleep at the 15mg dose (sedative properties are lost at higher doses)

Alleviates anxiety 

Low risk of sexual problems

Can be used off licence as a sleeping tablet or to augment treatment with another AD 

Mirtazapine may have a faster onset of action than some other antidepressants

Weight gain & appetite increased 

 

 

Bupropion

Atypical antidepressants

Bupropion may be associated with modest weight loss and not associated with sexual dysfunction

May be helpful for depressed patients who feel lethargic or fatigued

Contraindicated in patients with a seizure disorder;

Seizure risk with higher bupropion doses and appears to be a dose-related effect.

Extended-release and sustained-release bupropion formulations have a lower peak blood level and are associated with a lower incidence of seizures 

Bupropion may have a greater effect on potent CYP450 enzyme inhibition (CYP2D6) and lead to drug interactions  

Amitriptyline,
Clomipramine,
Imipramine
and Trimipramine

 

Tertiary amine TCAs

Can be used at lower doses to help sleep and is also helpful in neuropathic pain, can help detrusor muscle stability and migraines

TCAs are first generation (older) antidepressants and are rarely used as initial treatment

Lower cost agents that can be used second or third line if newer antidepressants such as SSRIs or SNRIs are not effective

Tertiary amines tend to have more bothersome side effects than secondary amines due to anticholinergic effects (e.g., constipation, dry mouth, blurred vision) and more a more sedating effect

Excessive doses of TCAs can lead to cardiac toxicity such as arrhythmias (fast or irregular heart rate), seizures, and orthostatic hypotension, leading to falls and possible injury

Most TCAs are not recommended  for elderly or severely depressed patients at risk for suicide due to the risk for overdose with TCAs

Nortriptyline

Secondary amine TCA

Better tolerated than other TCAs

 

Isocarboxacis,
Phenelzine,
Selegeline and
Tranylcypromine

 

MAOIs

Should normally be prescribed only by specialist mental health professionals

May be used for patients with severe depression that does not respond to several other antidepressant treatments first

Phenelzine may cause less insomnia than tranylcypromine.

Tranylcypromine causes less weight gain, sedation, and sexual dysfunction than phenelzine 

Severe side effects

Dietary interactions; high amounts of tyramine such as dried fruits, red wine, cheese, pickles, smoked or processed meats, ripe figs, fava beans. The combination may lead to an increase in blood pressure, headache, nausea and vomiting, confusion, seizures, or death. Avoid tyramine for 2 weeks after discontinuation of a MAOI.

Possibility of serotonin syndrome. Use caution when starting or stopping MAOI treatment to avoid a hypertensive crisis or serotonin syndrome

aripiprazole,
olanzapine,
risperidone and quetiapine

 

Atypical antipsychotics

Used to treat schizophrenia and bipolar disorder

some atypical (second generation) antipsychotics are approved as an add-on therapy for patients who do not have an optimal response to first-line depression treatment with a single agent.

often combined wit SSRIs

lower doses for unipolar major depression compared to doses for schizophrenia or bipolar depression.

weight gain, blood sugar increases, diabetes, metabolic syndrome and lipid changes (high cholesterol). Patients should be monitored for these effects

All antipsychotics are associated with an increased risk of death when used in elderly people, especially those with dementia-related psychosis, and they are not approved for this use

Dosulepin

Do not initiate

Evidence supporting its tolerability relative to other antidepressants is outweighed by the increased cardiac risk and toxicity in overdose

St John’s wort

Evidence that it is as effective as traditional antidepressants 

Available to purchase OTC

Unknown interactions

Lack of consistency of dosing in medications available

Lithium

Should normally be prescribed only by specialist mental health professionals

U&E & LFTs before treatment and 6-monthly thereafter, consider ECG monitoring if high risk for CV disease
Prazosin and doxazosin 

antihistamines which can help with nightmares in PTSD - start with 1mg nocte and increase by 1mg every month upto 12mg.

 

 

Side effects

Drug Anticho-linergic Cardiac Postural Hypo-tension Nausea Sedation Insomnia Procon- vulsant Sexual Dysfunction Weight Gain Withdrawal Symptoms Inhibition of Hepatic QT Interval Prolon-gation  Toxicity in Over-dose Specific Problems
 
Sertraline * * ** *** * *** * ***  ** *** ** * * All SSRIs Can: a. Increase nervouseness in first three days of treatment  b. Possibly increase risk of suicide attempts in depressed chldren and adolescents c. increased risk of gastrointestinal bleeding.
Citalopram * * ** **** * *** * ***  ** *** ** **  *
Fluoxetine * * ** ***  * ***  * ***  ** U **** * *
Escitalopram * * ** ***  * ***  * ***  ** ***  ** ** *
Paroxetine * * ** ***  * ***  * **** ***  **** **** * *
Vortioxetine * * ** *** * ** *** * * * * * *
Mirtazapine * * ** * ***  ** ***  ***  **** ** U   * Blood Dyscrasia
Trazodone ** ** ***  **** ***  ***  * ***  **** U U   *  
Venlafaxine * ***  ** ***  ** ***  ** ***  **   **   ** Hypertension. BP and ECG monitoring suggested.
Duloxetine * * ** **** ** ***  U ***  ** U ** * U
Amitriptyline **** **** **** ***  **** ** ***  ***  **** ***  **** ***  ***  All TCAs: Potentially carditoxic in therapeutic dosage and in overdose.
Clomipramine **** ***  **** ***  ***  ***  ***  **** ***  ***  **** ** *** 
Imipramine ***  ***  **** ***  ** ***  ***  ***  ***  ***  ****   *** 
Lofepramine ***  ** ***  ** ** U * ***  **** U U   *  
Phenelzine ** ** **** ***  ** ***  * ** ***  **** **   ***  Hypertensive crisis with sympathomimetics.
Moclobemide ** * ** ** * ***  U ** ** ** **   *  

 

Dosages for depressive illness

Antidepressant

Start dose Adults <65y

Max dose Adults <65y

Start dose Adults >65y

Max dose Adults >65y

Hepatic impairment

Renal Impairment

Citalopram

20mg

40mg

10mg

20mg

20mg

No information available for eGFR less than 20 mL/min; start at reduced dose and titrate slowly

Escitalopram

10mg

20mg

5mg

10mg

10mg

Caution if eGFR less than 30 mL/ min: Start at reduced dose and titrate slowly

Sertraline

50mg

200mg

50mg

200mg

Reduce dose or increase dose interval in mild to moderate impairment.

Use with caution
Fluoxetine  20mg 60mg 20mg 40mg Caution  due to prolonged half-life No adjustment needed
Paroxetine  20mg 50mg 20mg 40mg Caution due to prolonged half-life  In severe impairment: initial dose 10mg max dose 40mg 
Venlafaxine  75mg 375mg 75mg 375mg caution (inter-individual variability in clearance; limited information available in severe impairment) Reduce dose by 50% in mild to moderate impairment more than 50% in severe impairment
Duloxetine  60mg 120mg 60mg 120mg Avoid Avoid if eGFR less than 30 mL/minute/1.73 m2
Mirtazipine  15mg 45mg 15mg 45mg Manufacturer advises caution (risk of increased plasma concentration, no information available in severe impairment). Clearance reduced by 30% if eGFR less than 40 mL/minute/1.73 m2; clearance reduced by 50% if eGFR less than 10 mL/minute/1.73 m2.
Trazoone  150mg 600mg 100mg 600mg Manufacturer advises caution, particularly in severe impairment (increased risk of side-effects). Use with caution in severe impairment.
Vortioxetine  10mg 20mg 5mg 20mg Manufacturer advises caution in severe impairment (no information available) Manufacturer advises caution in severe impairment—limited information available.
Bupropion  150mg  300mg 150mg  150mg  Manufacturer advises reduce dose to 150 mg daily in mild to moderate impairment Reduce dose to 150 mg daily in mild 75mg in moderate and 150mg every 3 days in severe
Amitriptiline 50 mg in 2 divided dose  150mg in two divided doses 10mg daily  100-150mg  Manufacturer advises use with caution in mild-to-moderate impairment; avoid in severe impairment. Reduce dose by 50% in geriatric patients
Clomipramine  10mg  250mg 10mg  75mg  Manufacturer advises caution; avoid in severe impairment (risk of hypertensive crisis). Reduce dose by 50% in geriatric patients
Trimipramine  50mg  300mg 10mg   150mg  Manufacturer advises avoid in severe impairment. Reduce dose by 50% in geriatric patients
Nortriptiline  25mg   150mg 25mg  50mg in divided doses  Manufacture advises avoid in severe impairment.  

                                       

Most effective 

 

Best tolerated

 

Effective and well tolerated

 Amitriptyline

Escitalopram

Mirtazapine

Paroxetine

Venlafaxine

Vortioxetine

Citalopram

Escitalopram

Fluoxetine

Sertraline

Vortioxetine

Escitalopram

Vortioxetine

Least effective

Least well tolerated

Less effective and poorly tolerated

Fluoxetine

Fluvoxamine

Reboxetine

Trazodone

Amitriptyline

Clomipramine

Duloxetine

Fluvoxamine

Reboxetine

Trazodone

Venlafaxine

Fluvoxamine

Reboxetine

Trazodone

* effectiveness difference between the antidepressants was most noticeable in the head-to-head trials and less noticeable in placebo-controlled trials

  References

 

  • The DTB reports a study that tried to work out how many people who had not responded to an antidepressant at 4 weeks would get a benefit if the same one was continued until 8 weeks.
  • Always ask about alcohol history, and take this into account when considering treatment options, particularly drug options
  • The importance of continuing once remission achieved.
  • The risk and nature of discontinuation symptoms (especially with paroxetine and venlafaxine).
  • Review the patient after 2w, and then 2–4 weekly for the first 3m. See review section
  • If <30y or risk of suicide, see more often (e.g. after 1w).
  • If significant side-effects early in treatment:
  • Continue with close monitoring if acceptable to patient.
  • Stop/change antidepressant.
  • Offer short-term (2w) benzodiazepine to help anxiety/agitation, but not in those with chronic anxiety ( or previous drug dependence or alcohol dependence issues) as they are more likely to develop dependence
  • Expect initial improvement after 2–4w. If no/minimal response after 3–4w, increase support and consider:
  • If inadequate response after 6–8w, consider switching to an alternative antidepressant 
  • Remember that a single antidepressant usually gives fewer side-effects than combinations of antidepressants.
  • When switching antidepressants:
  • If one SSRI has been ineffective, try an alternative SSRI.
  • If that is ineffective, try an alternative class of antidepressants (venlafaxine, tricyclic, MAOI). 

fluoxetine paroxetine venlafaxine Sertraline Citalopram Escitalopram Duloxetine Bupropion phenelzine tranylcypromine reboxetine vortioxetine moclobemide amitriptyline clomipramine imipramine lofepramine nortriptyline trimipramine trazodone Mirtazipine Isocarboxacis Selegeline aripiprazole risperidone quetiapine

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