DR MAX PEMBERTON’s ultimate guide to the best antidepressant for you

When it comes to treating depression, one size definitely does not fit all. There are many different types of antidepressants and while they can be life-changing for people with moderate to severe depression, they’re not the answer for everyone.

Talking therapies can often be effective for milder depression but medication is essential for people with severe symptoms.

The key is matching the right treatment to the right person.

Just how different antidepressants can be was highlighted by a recent ground-breaking study published in The Lancet.

Researchers from King’s College London and the University of Oxford, who analysed more than 150 studies involving over 58,000 patients, found significant differences in side-effects – including weight changes, blood pressure, heart rate and cholesterol – over the first eight weeks of treatment.

While this might seem a short time frame (many people take antidepressants for months or even years), the early weeks are when side-effects typically emerge and when people are most likely to stop taking pills.

Understanding what to expect in this crucial period can help people stick with treatment.

There are other factors a doctor will consider, including how sedating a drug is, whether it helps with other problems such as pain or sleep, how difficult it is to come off the medication when the time comes as well as sexual side-effects.

Sexual dysfunction can often occur with commonly prescribed antidepressants, SSRIs (selective serotonin reuptake inhibitors), persisting throughout treatment.

In rare cases, sexual side-effects can continue even after stopping the medication – a condition known as post-SSRI sexual dysfunction.

Your age, weight, blood pressure, other health conditions and personal priorities all matter when choosing an antidepressant – a good doctor will discuss these with you.

NICE guidelines recommend doctors start with an SSRI, as these tend to be well-tolerated and effective for most people. Other SSRIs, or another class of antidepressant, will be considered if these don’t work.

Every medicine comes with side-effects. But what one person experiences as an unwanted side-effect can actually be just what another needs.

Take mirtazapine, which commonly increases appetite and causes weight gain. For the elderly patient who’s lost 2st because depression has robbed their appetite, that side-effect becomes therapeutic.

Side-effects are common in the first few weeks, especially nausea, headache or a change in bowel habits. These usually improve as your body gets used to the new medication.

That said, don’t suffer in silence if your antidepressant isn’t suiting you. There are alternatives. But never stop taking an antidepressant without consulting your doctor.

Stopping these drugs suddenly can cause unpleasant withdrawal effects, including dizziness and electric shock-type sensations – and significantly increases the chances of your depression returning.

The key is to taper off slowly (reducing the dose gradually over weeks or months). A major review published last week in the Lancet Psychiatry found that slowly tapering, alongside psychological support, is the most effective way for stopping.

To help you with these discussions, I’ve drawn on my years of experience as a consultant psychiatrist – and the findings of the new Lancet study – to compile this expert guide to the most commonly prescribed antidepressants in the UK.

CITALOPRAM (BRAND NAME CIPRAMIL)

Widely prescribed SSRI, considered a gentler antidepressant. It has fewer interactions with other medications and fewer side-effects than some other SSRIs. A good starting point.

BEST FOR: 

• First-time users.
• People with high blood pressure (has minimal effect).
• Those concerned about cholesterol (neutral effect).
• Older adults, as it’s generally well-tolerated.

THINK TWICE IF:

• You have heart rhythm problems (can affect heart’s electrical activity at higher doses).
• You’re on multiple medications (such as those that also affect heart rate).
• Sexual function is important to you.

NEW STUDY FOUND: One of the better tolerated SSRIs overall. Minimal impact on weight, blood pressure and cholesterol. Like other SSRIs, commonly causes sexual side-effects including reduced libido, delayed orgasm or difficulty achieving orgasm.

ESCITALOPRAM (CIPRALEX)

An SSRI that’s essentially a refined version of citalopram – it’s not stronger, but it’s more purified, so you can take a lower dose for the same effect, potentially reducing side-effects.

BEST FOR: 

• Anxiety disorders, as well as depression.
• People with high blood pressure (minimal effect).
• Those concerned about cholesterol (neutral effect).
• When citalopram hasn’t quite done the job.

THINK TWICE IF: 

• You have heart rhythm issues (similar concerns to citalopram).
• You’re taking other medications that affect heart rhythm.
• Sexual function is important to you.

NEW STUDY FOUND: Very similar profile to citalopram. Generally well-tolerated with minimal effects on weight, blood pressure and cholesterol. Sexual difficulties including reduced desire, problems with arousal and delayed or absent orgasm.

PAROXETINE (SEROXAT)

An SSRI that’s particularly effective for anxiety disorders.

BEST FOR: 

• Anxiety, particularly social anxiety and panic disorder.
• People who need a sedating antidepressant (can help with sleep).
• Those who haven’t responded to other SSRIs.

THINK TWICE IF: 

• You’re concerned about cholesterol (it has been linked to higher cholesterol).
• You’re planning to come off medication soon (harder to withdraw from than other SSRIs).
• You have any blood pressure concerns.
• Sexual function is important to you.

NEW STUDY FOUND: Can affect cholesterol levels and blood pressure. More likely to cause sedation and weight gain than some other SSRIs.

Known for being trickier to stop – withdrawal symptoms can be more pronounced, so reduction needs to be gradual.

Often cited as causing more sexual dysfunction than other SSRIs. For most, sexual function returns to normal after stopping the medication, though this can take weeks. Problems may persist in rare cases.

VENLAFAXINE (EfFEXOR)

An SNRI (serotonin-norepinephrine reuptake inhibitor) which targets two brain chemicals rather than one. Serotonin is thought to help regulate mood, sleep and anxiety; while norepinephrine is involved in energy, alertness and concentration.

BEST FOR: 

• More severe depression that hasn’t responded to SSRIs.
• Depression with fatigue and low energy.
• Some chronic pain conditions.
• When you need something more powerful.

THINK TWICE IF: 

• You have high blood pressure (raises blood pressure, particularly at higher doses).
• You’re concerned about cholesterol (has been linked to raised cholesterol).
• You have heart problems (increases heart rate).
• You’re concerned about weight gain.
• Sexual function is important to you.

NEW STUDY FOUND: Significantly raises blood pressure, increases heart rate and affects cholesterol levels. Effects are dose-related and need monitoring. Can also cause more pronounced withdrawal symptoms if stopped suddenly, so important to taper slowly. Sexual side-effects occur but may be less frequent than with SSRIs.

DULOXETINE (CYMBALTA)

Another SNRI, but with additional licensed uses, such as stress incontinence. This is often my go-to for people who haven’t got on with SSRIs.

BEST FOR: 

• When you need an antidepressant that also addresses pain (particularly back pain or arthritis).
• Diabetic nerve pain.

• Stress incontinence in women – duloxetine strengthens the muscles that control the bladder by increasing norepinephrine activity in the nerves that supply them.

THINK TWICE IF: 

• You’re concerned about cholesterol (linked to raised cholesterol).
• You have liver problems (processed by the liver).
• You have uncontrolled high blood pressure.
• Sexual function is important to you.

NEW STUDY FOUND: Raises cholesterol levels. Can also cause nausea, dry mouth and constipation initially. Like venlafaxine, needs careful monitoring if you have blood pressure issues. Sexual dysfunction can occur, but is often less of an issue than with SSRIs.

MIRTAZAPINE (ZISPIN)

A tetracyclic antidepressant that works differently from SSRIs and SNRIs. Rather than blocking the reuptake of serotonin, mirtazapine blocks receptors (called alpha-2 receptors) that usually limit how much serotonin and norepinephrine your brain releases.

BEST FOR: 

• Depression with severe insomnia, as it can be very sedating. Note, this is more sedating at lower (not higher) doses.
• People who’ve lost their appetite or who are losing weight.
• When SSRIs have caused too many side-effects.
• Older adults who need help with sleep and appetite.

THINK TWICE IF: 

• You’re concerned about weight gain (can cause significant weight gain, often 2kg or more).
• You need to stay alert during the day (very sedating for many).
• You’re already overweight or have diabetes.

NEW STUDY FOUND: Significant weight gain and increased appetite are common. Very sedating, which is helpful for sleep but can leave some people feeling groggy. Importantly, has significantly fewer sexual side-effects than SSRIs – a major advantage if sexual function is important.

AMITRIPTYLINE 

Older type of antidepressant, known as a tricyclic. Increases serotonin and norepinephrine like newer antidepressants, but also affects histamine and acetylcholine, which is why it’s more sedating and has more side-effects like dry mouth and constipation. It can be dangerous in overdose, so not advised for those who feel suicidal.

BEST FOR: 

• Depression with chronic pain or nerve pain.
• Severe insomnia (it is very sedating).
• Migraine prevention.
• When modern antidepressants haven’t worked. Sometimes used in low doses for anxiety or sleep.

THINK TWICE IF: 

• You’re concerned about weight gain.
• You have heart problems (raises heart rate and blood pressure).
• You have high blood pressure.
• You have glaucoma or prostate problems – the drug has ‘anticholinergic’ effects, meaning it blocks a chemical messenger called acetylcholine. This can worsen glaucoma by increasing pressure in the eye, and can make it harder to urinate if you have an enlarged prostate.
• You’re older (increased risk of falls and confusion).

NEW STUDY FOUND: Significant effects on weight (gain), heart rate (increases) and blood pressure (increases). Also causes dry mouth, constipation, blurred vision and drowsiness – all caused by the drug-blocking acetylcholine. Despite these side-effects, it remains valuable for pain and sleep problems. Generally causes fewer sexual side-effects than SSRIs.

NORTRIPTYLINE

Another tricyclic antidepressant but often better tolerated than amitriptyline.

BEST FOR: 

• Depression in older adults (it is better tolerated than amitriptyline).
• Chronic pain and nerve pain.
• When you need a tricyclic, but can’t tolerate amitriptyline.

THINK TWICE IF: 

• You have heart problems (significantly increases heart rate – highest increase in the study).
• You have high blood pressure (raises blood pressure).
• You have glaucoma.
• You’re at risk of falls.

NEW STUDY FOUND: Major effects on blood pressure (increases by up to 11mmHg) and heart rate (speeds it up significantly). Compared to amitriptyline, nortriptyline causes less dry mouth, constipation and confusion, so doctors often prefer it for older patients who need a tricyclic antidepressant. It tends to cause fewer sexual problems than SSRIs.

AGOMELATINE (VALDOXAN)

Newer antidepressant (licensed in the UK in 2008) that works on receptors in your brain that respond to melatonin, the hormone that regulates your sleep-wake cycle.

BEST FOR: 

• People concerned about weight (linked to loss in the study – up to 2.4kg over eight weeks).
• Depression with disrupted sleep – because it works on melatonin receptors, it can help reset your body clock.
• When avoiding sexual side-effects is a priority (minimal impact).
• Those who’ve had troublesome side-effects with other options.

THINK TWICE IF: 

• You have liver problems (requires monitoring).
• You’re on certain other medications (e.g. the antidepressant, fluvoxamine; or antibiotic, ciprofloxacin), which can increase agomelatine levels in the blood. These drugs slow down the liver enzyme that breaks down agomelatine, meaning the medication builds up to higher levels in your blood than intended – which increases the risk of side-effects.
• You need an antidepressant with long-term data (less long-term evidence).

NEW STUDY FOUND: Associated with weight loss rather than gain; significantly fewer sexual side-effects than SSRIs. Main consideration is liver function, which needs checking before starting and monitoring with blood tests during treatment (as agomelatine can, in rare cases, cause liver inflammation).

VORTIOXETINE (BRINTELLIX)

A newer antidepressant that works on multiple serotonin receptors. While SSRIs block the reuptake of serotonin, vortioxetine stimulates or blocks different serotonin receptor subtypes. This may explain why it seems to have benefits for concentration. Less commonly prescribed and usually only by psychiatrists (GPs are less familiar with it), after people have tried other options. Good option, especially for older people.

BEST FOR: 

• Depression with cognitive problems (difficulty concentrating, memory issues, mental fog).
• People concerned about sexual side-effects (generally better tolerated than SSRIs in this regard).
• Older adults (regarded a safer choice).
• When you need a generally well- tolerated antidepressant.

THINK TWICE IF: 

You’re on certain other medications, particularly MAOIs (an older type of antidepressant now rarely used) or other medications that increase serotonin – including other antidepressants, certain painkillers such as tramadol and the migraine drugs, triptans.

You have a history of bleeding issues.

NEW STUDY FOUND: Generally well- tolerated, with no significant impact on weight, blood pressure and heart rate. Sexual side-effects are less common than with SSRIs. Nausea is the most frequently reported side-effect but usually settles after a few weeks. Particularly valued for having minimal negative impact on cognitive function – and may even improve concentration and memory.

FLUOXETINE (PROZAC) 

Around since the 1980s, this SSRI is probably the most famous antidepressant.

BEST FOR: 

• People concerned about weight gain (unlike many antidepressants it’s unlikely to cause weight gain).
• Those who’ve had problems with withdrawal from other antidepressants. All drugs have a ‘half-life’ – the time it takes for it to leave your body. Fluoxetine has a long half-life of four to six days (compared with a day for other SSRIs), so leaves your system gradually rather than abruptly. This makes withdrawal symptoms less likely.
• Bulimia nervosa (the eating disorder associated with secretive bouts of overeating; the drug is licensed for this).
• Helping with motivation. The drug tends to increase energy and alertness, which some find helpful for getting things done.

THINK TWICE IF: 

• You have high blood pressure (it can raise blood pressure).
• You’re very anxious (it can initially increase anxiety and jitteriness).
• You’re taking other medications (long half-life means more drug interactions).
• Sexual function is important to you.

NEW STUDY FOUND: Associated with weight loss but increased blood pressure. More energising than other SSRIs, so useful for people who feel unmotivated, but can increase jitteriness in others initially. Sexual dysfunction is common, though some people find it less of an issue than with paroxetine (see main story).