Category: Antidepressants

Do antidepressant do more harm than good?

While people are no more depressed now than they were 20 years ago, antidepressant use has tripled in this period.

Despite the surge, relatively little is known about how they work.

There is scant evidence that they ‘correct a chemical imbalance in the brain’, as drug marketers claim.

This raises many question, including:

• Do antidepressants do more harm than good?
• Do they really improve people’s quality of life compared with not taking them?
• How easy or hard is it to come off them?
• What is the best way to quit?

Below are 7 studies from the members-only section of PsyBlog that try to answer these questions, and more:

(If you are not already, find out how to become a PsyBlog member here.)

1. Antidepressants: Pros And Cons And How They Should Be Prescribed
2. How Antidepressants Affect Long-Term Quality Of Life
3. How Stopping Antidepressants Affects Relapse Risk
4. Depression NOT Caused By Low Serotonin Levels, Large Review Finds
5. The Real Risks Of Taking Antidepressants
6. The Best Way To Quit Antidepressants
7. Antidepressants Kill Positive Emotions Too: Why That’s Dangerous

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For the first few weeks antidepressants have a strange side-effect researchers are trying to tackle.

It is popularly believed that SSRIs, like Prozac and Zoloft, only produce good feelings.

In fact, in the first few weeks of treatment, common antidepressants can cause increased anxiety and fear.

Serotonin — the neurotransmitter that is boosted by SSRIs — is even linked to suicidal thinking, especially in young people.

Research, though, could provide a clue as to how the effect can be reduced.

The serotonin-activated pathways in the brains of mice that lead to anxiety have been traced.

The circuit could be crucial to how SSRIs produce short-term anxiety.

Professor Thomas L. Kash, who led the research, said:

“The hope is that we’ll be able to identify a drug that inhibits this circuit and that people could take for just the first few weeks of SSRI use to get over that hump.

More generally, this finding gives us a deeper understanding of the brain networks that drive anxiety and fear behavior in mammals.”

Having identified the crucial circuit in the brain, the researchers moved on to trying to block it.

They were able to this with a ‘CRF blocker’, but as this research was in mice, it is not clear if the same result would be seen in humans.

Professor Kash said:

“It’s logical that it would since we know SSRIs can induce anxiety in people, and the pathways in these brain regions tend to be very similar in mice and humans.”

Professor Kash said:

“Other researchers are working to develop better CRF-inhibiting compounds, so that’s one potential direction to take, but there are others.

We’re now looking at the various proteins expressed by these BNST neurons, and we’re hoping to identify a receptor that is already targeted by established drugs.

One of them might be useful for people as they start taking SSRIs.”

The study was published in the journal Nature (Marcinkiewcz et al., 2016).

SSRI antidepressants such as Prozac and Zoloft can increase anxiety in the first few weeks.

Around 100 million people around the world take antidepressants like Prozac and Zoloft.

However, few are aware beforehand that antidepressants can worsen anxiety in the first few weeks of use.

Until recently scientists have found the side-effect mysterious.

Now, though, they have identified an anxiety circuit in the brain that responds to serotonin.

The study’s findings help underline the fact that serotonin does not just promote good feelings, despite what many think.

Professor Thomas L. Kash, who led the study, said:

“The hope is that we’ll be able to identify a drug that inhibits this circuit and that people could take for just the first few weeks of SSRI use to get over that hump.

More generally, this finding gives us a deeper understanding of the brain networks that drive anxiety and fear behavior in mammals.”

Anxiety worsened by SSRIs like Prozac And Zoloft

Studies have long suggested that serotonin can actually have negative effects on mood.

Younger people seem particularly vulnerable.

Scientists at the University of North Carolina (UNC) School of Medicine have now mapped out the pathway in the brain that is sensitive to serotonin and is linked to anxiety.

The regions of the brain are called the dorsal raphe nucleus (DRN) and the bed nucleus of the stria terminalis (BNST).

After activating these areas in mice using serotonin, the scientists observed anxiety-like behaviours.

Testing Prozac on these mice also showed that it made them more anxious.

Next the researchers hope to find a way of blocking the anxiety-inducing effects of antidepressants.

However, it will first need to be confirmed that human brains operate in a similar way to mice in this regard.

Professor Kash said:

“It’s logical that it would, since we know SSRIs can induce anxiety in people, and the pathways in these brain regions tend to be very similar in mice and humans.”

The study was published in the journal Nature (Marcinkiewcz et al., 2016).

Study tests if antidepressants really help depressed people feel better in the long-term.

Over nine years, depressed people were better off if they had no treatment at all than if they took antidepressants, research finds.

In addition, depressed people that got adequate treatment without medication did better nine years later than those who got adequate treatment with medication.

It may be that taking antidepressants causes more harm than no treatment whatsoever in the long run.

These effects could be the result of many factors that others have suggested.

For example, coming off antidepressants after taking them for a time can be difficult due to withdrawal effects.

Antidepressants may also permanently change the way neurotransmitters in the brain work.

Alternatively, perhaps most of the effect of antidepressants is down to placebo.

Studies have found, for example, that the science of antidepressants is based on backward facts.

Professor Jeffrey R. Vittengl, the study’s author, writes:

“…treatment including medication may have worsened depression in the long run.

Until mechanisms of benefits and harms are better understood, these findings argue for using antidepressant medication only if short-term benefits (e.g., reducing active suicide risk) are likely to outweigh delayed consequences.”

The short-term benefits of antidepressants are well-known.

They can help people who are in crisis.

However, the studies that test the effects of antidepressants usually only follow them for a year or two.

Antidepressants don’t help much in the long-term

The study looks at how people do over 9 years.

It included data from over 15,000 people in the US.

None of them were in hospital, but around 10% had experienced a major depressive episode in a one-year period.

Around 38% of these people received no treatment for their depression.

Only 4% received adequate treatment that did not include antidepressant medication.

However, 13% received adequate treatment that included medication.

Professor Vittengl found that medication was linked to doing worse over the long run:

“This pattern suggests possible long-term iatrogenic effects of antidepressants.

For example, antidepressant medications may recruit processes that oppose and eventually overwhelm short-term benefits resulting in loss of efficacy, resistance to retreatment, paradoxical effects, and withdrawal syndromes, perhaps via disruption of homeostatic control of monoamine neurotransmitters.”

The study was published in the journal Psychotherapy and Psychosomatics (Vittengl, 2017).

A popular herbal antidepressant has dangerous side-effects.

Kratom, a herbal antidepressant also used for pain relief and other conditions, is NOT safe, research finds.

Kratom, which is a supplement derived from a southeast Asian tree, is used by some to treat opioid addiction.

Kratom is sold as a mood-enhancer, energy booster and pain-reliever.

However, a new analysis of the US National Poison Data System, finds it has a worrying range of side-effects.

The research suggests that kratom is not reasonably safe and poses a threat to public health.

The study of of 2,312 incidents of kratom exposure found that the most common side-effects of kratom were:

• agitation (18.6 percent),
• tachycardia, a racing heart (16.9 percent),
• drowsiness (13.6 percent),
• vomiting (11.2 percent),
• and confusion (8.1 percent).

More serious side-effects were also reported:

• seizure (6.1 percent),
• withdrawal (6.1 percent),
• hallucinations (4.8 percent),
• respiratory depression (2.8 percent),
• coma (2.3 percent),
• and cardiac or respiratory arrest (0.6 percent).

The supplement was listed as a cause of death in the case of four people.

Kratom is classified as a dietary supplement, so not regulated by the FDA in the US.

The active ingredient of Kratom is mitragynine, which binds to opioid receptors in the brain.

This may cause a pain relieving and sedative effect.

Dr William Eggleston, the study’s first author, said:

“Although it is not as strong as some other prescription opioids, kratom does still act as an opioid in the body.

In larger doses, it can cause slowed breathing and sedation, meaning that patients can develop the same toxicity they would if using another opioid product.

It is also reported to cause seizures and liver toxicity.

Kratom may have a role in treating pain and opioid use disorder, but more research is needed on its safety and efficacy.

Our results suggest it should not be available as an herbal supplement.”

Kratom is already illegal, or only semi-legal in many countries, including the UK, Denmark, Finland, Thailand and Australia.

Some US states have banned the herb, including Alabama, Arkansas, Indiana, Rhode Island, Vermont, and Wisconsin.

The study was published in the journal Pharmacotherapy (Eggleston et al., 2019).

The most effective antidepressants revealed by a review of 522 different studies involving 116,477 people.

Most antidepressants do work, according to a review of 522 different studies involving 116,477 people.

The review — published in the medical journal The Lancet — found that 21 common antidepressants beat placebos in strictly controlled tests.

The study’s first author, Dr Andrea Cipriani, believes this is the ‘final answer’ to the controversy over whether or not antidepressants work.

The study found that most antidepressants were better than placebo for moderate to severe depression.

However, set against this, it is well-known that common antidepressants have little to no effect for up to 50 percent of people.

5 most effective antidepressants

The five most effective antidepressants, according to this research, are:

• Amitriptyline (known as Elavil and others)
• Agomelatine (known as Melitor, Thymanax and Valdoxan)
• Escitalopram (known as Cipralex, Lexapro and others)
• Mirtazapine (known as Remeron and others)
• Paroxetine (known as Paxil, Pexeva, Seroxat and others)

The four least effective antidepressants (although they still worked) were:

• Fluoxetine (known as Prozac, Sarafem, Adofen and others)
• Fluvoxamine (known as Faverin, Fevarin, Floxyfral, Dumyrox and Luvox)
• Reboxetine (known as Edronax and others)
• Trazodone (known as Desyrel, Oleptro, Trazorel and many others)

The study of the most effective antidepressant — known as a meta-analysis — brings together 522 different drug trials.

Some of these trials involved previously unpublished data from pharmaceutical companies.

Professor Carmine Pariante, at the London Institute of Psychiatry, who was not involved in the research, said:

“…the paper analyses unpublished data held by pharmaceutical companies, and shows that the funding of studies by these companies does not influence the result, thus confirming that the clinical usefulness of these drugs is not affected by pharma-sponsored spin.”

Professor Allan Young, Director of the Centre for Affective Disorders at London’s KCL, who was not involved in the research, said:

“…we should be aware that these findings only apply to major depressive disorder and are calculated from group data so individual patients may differ significantly in their responses.

A range of treatment choices should therefore be maintained.

Also a lot of “antidepressants” are used for other disorders (such as anxiety or OCD) or off-label (where the drug is prescribed for something other than the original condition for which it was officially approved) and this evidence does not apply in these instances.

However, the top line is that these findings should be considered good news as they confirm existing evidence that antidepressants do work and, for most people, the side-effects are worth it.”

Most of the studies involved using antidepressants for around 8 weeks — so the results don’t tell us anything about using them long-term.

They also cannot tell us which drugs are most suitable for individuals.

Are the side-effects worth it?

Although the side-effects of antidepressants are frequently pointed out, Professor Anthony Cleare at KCL (also not involved in the research) believes the benefits are worth it:

“…it is interesting that for almost all antidepressants, patients are no more likely to stop treatment early when taking an antidepressant than when taking a placebo.

Some treatments were even better tolerated than placebo.

This suggests that, overall, patients judge that the greater effect of antidepressants in relieving depression counterbalances any side effects.

Other scientists are not so sure.

For example, one review looking at antidepressants’ effect on the whole body concludes they may do more harm than good, although it may be that these ‘side-effects’ can be attributed to the underlying psychiatric conditions people are being treated for, rather than the drugs themselves.

Surveys of antidepressants side-effects also frequently find higher than expected levels of emotional numbness, sexual problems and even suicidal thoughts associated with the medication.

Indeed, it is common, in the first few weeks of treatment, for common antidepressants to cause increased anxiety and fear.

→ Read on: Antidepressants: Pros And Cons And How They Should Be Prescribed

The study was published in the journal The Lancet (Cipriani et al., 2018).

A little-known antidepressant side-effect on emotions and motivation.

People taking antidepressants find it harder to identify their feelings, research finds.

The drugs may cause emotional blunting, lower levels of empathy and even apathy.

The difficulty identifying emotions and apathy could be two sides of the same coin.

SSRI antidepressants in particular are sometimes said to make people indifferent: apathetic towards their emotions and any activities.

People taking the drugs feel less motivation and less emotion — whether positive or negative.

For the study, 57 people taking antidepressants were compared to a control group of 441 people.

The results showed that people taking the antidepressants were more likely to have trouble identifying their feelings.

The study’s authors point out that their research doesn’t necessarily show that taking antidepressants causes this side-effect.

However, it is thought that up to one in five people taking antidepressants have emotional side-effects.

Some studies, though, suggest the rates of apathy and emotional blunting after taking SSRI antidepressants could be even higher, perhaps approaching 50%.

The antidepressants people were taking in the study were mostly SSRIs, which target the serotonin system and include most modern antidepressants such as Prozac, Zoloft, Paxil and many, many more.

Some were also taking older style tricyclic antidepressants, such as clomipramine.

The study was published in the journal Experimental and Clinical Psychopharmacology (Kajanoja et al., 2018).