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Antidepressants and Autism Ranking: Mildly Hazardous Unable to rate

Anti-depressant tablets

Antidepressants are types of medications which are normally used to treat people with moderate to severe depressive illness. They may also be used to treat people with a range of other conditions including

- Severe anxiety and panic attacks
- Obsessive compulsive disorders
- Chronic pain
- Eating disorders
- Post-traumatic stress disorder.

There are several types of antidepressants including

- Selective serotonin reuptake inhibitors (SSRIs)
- Selective serotonin reuptake enhancers (SSREs)
- Serotonin-noradrenaline reuptake inhibitors (SNRIs)
- Noradrenaline and specific serotonergic antidepressants (NASSAs)
- Tricyclic and tricyclic-like antidepressants (TCAs)
- Monoamine oxidase inhibitors (MAOIs).

Antidepressants are normally prescribed in combination with other treatments, such as talking treatments and lifestyle changes. 

Antidepressants are sometimes used to help people on the autism spectrum with mental health problems (such as depression and anxiety), with the core features of autism (such as restricted and repetitive behaviours and interests) and with other issues (such as challenging behaviours). 

Please note

The National Institute of Health and Care Excellence (NICE) made the following recommendations:

“Do not use antidepressant medication for the routine management of core symptoms of autism in adults.” (NICE, 2012)

“Do not use [antidepressants] for the management of core features of autism in children and young people.” (NICE, 2013)

Our Opinion

There is insufficient high quality research evidence to determine if antidepressants have any effect on the core features of autism, such as restricted, repetitive patterns of behaviour, interests, or activities.

There is insufficient high quality research evidence to determine if antidepressants have any effect on mental health problems, such as depression and anxiety, in people on the autism spectrum.

There is insufficient high quality research evidence to determine if antidepressants have any effect on other issues, such as challenging behaviours, in people on the autism spectrum.

There is evidence of significant side effects of some antidepressants in some people including in some individuals on the autism spectrum.

We believe that antidepressants should only be used in combination with other treatments, under specialist supervision, and where other measures prove insufficient.

When choosing a specific antidepressant medication, you should take into account any side effects, the costs, your preference, and your response to any previous treatment with an antidepressant.

Future research should determine which antidepressants are effective for the treatment of which issues in which individuals on the autism spectrum. It should compare antidepressants with other, non-medicinal interventions designed to tackle depression, anxiety and other issues in people on the autism spectrum. It should also investigate the optimal dosage and length of treatment for different individuals, while also investigating any long-term effects. 

Disclaimer

Please read our Disclaimer on Autism Interventions


Audience

According to the Royal College of Psychiatrists (2015), antidepressants are normally used to treat people with moderate to severe depressive illness (but not mild depression).

They may also be used to treat people with a range of other conditions including

  • Severe anxiety and panic attacks
  • Obsessive compulsive disorders
  • Chronic pain
  • Eating disorders
  • Post-traumatic stress disorder.

Antidepressants are sometimes used to help people on the autism spectrum with mental health problems (such as depression and anxiety), with the core features of autism (such as restricted and repetitive behaviours and interests) and with other issues (such as challenging behaviours). 

Aims and Claims

Aims

Antidepressants are normally used to treat people with moderate to severe depressive illness and a range of other conditions. 

Antidepressants are designed to work by boosting or prolonging the activity of particular brain chemicals, such as noradrenaline and serotonin, which are thought to be involved with regulating mood. However, according to Mind (2016), “... there is no scientific evidence that depression is caused by a chemical imbalance which is corrected by antidepressants.”

Claims

There have been various claims made for the use of antidepressants as a treatment for people on the autism spectrum.  For example,

  • Couturier and Nicolson (2002) reported that citalopram led to decreases in aggression, anxiety, stereotypies, and preoccupations
  • Hollander et al (2005) reported that fluoxetine was significantly better than placebo in decreasing repetitive behaviors and marginally superior to placebo in decreasing global autism severity
  • McDougle et al (1998) reported that sertraline was effective in reducing interfering repetitive and aggressive symptoms in adults with pervasive developmental disorders [autism]
  • Niederhofer (2003) reported that that parents and teachers reported perceived reductions in irritability, hyperactivity, inadequate eye contact and inappropriate speech when using tianeptine
  • Remington (2001) reported that clomipramine led to improvements in ‘autistic symptoms’, irritability and OCD-like symptoms 

Key Features

Antidepressants are types of medications which are normally used to treat people with moderate to severe depressive illness and a range of other conditions. 

Antidepressants are normally prescribed in combination with other treatments, such as talking treatments and lifestyle changes. This is because, according to the Royal College of Psychiatrists (2015),

“It is not enough just to take the pills. It is important to find ways of making yourself feel better, so you are less likely to become depressed again. These can include finding someone you can talk to, keeping physically active, drinking less alcohol, eating well, using self-help techniques to help you relax and finding ways to solve the problems that have brought the depression on.”

Types

There are several types of antidepressants including:

  • Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Cipramil), fluoxetine (Prozac) and sertraline (Lustral).
  • Selective serotonin reuptake enhancers (SSREs) such as tianeptine (Stablon).
  • Serotonin noradrenaline reuptake inhibitors (SNRIs) such as such as duloxetine (Cymbalta and Yentreve).
  • Noradrenaline and specific serotonergic antidepressants (NASSAs), such as mirtazapine (Zispin).
  • Tricyclic and tricyclic-like antidepressants (TCAs) such as amitriptyline (Tryptizol), clomipramine (Anafranil) and imipramine (Tofranil).
  • Monoamine oxidase inhibitors (MAOIs) such as isocarboxazid (Marplan), phenelzine (Nardil) and tranylcypromine (Parnate).

In practice, you are more likely to be prescribed with the newer antidepressants (such as the SSRIs and the SNRIs) than the older antidepressants (such as the tricyclics and the MAOIs) because they tend to have fewer side effects.

Mechanism – how they work

According to Mind (2016),

“Antidepressants work by boosting or prolonging the activity of particular brain chemicals, such as noradrenaline and serotonin, which are thought to be involved with regulating mood.

“Noradrenaline and serotonin are neurotransmitters. This means that they pass messages between nerve cells in your brain, and between nerves and other target organs in the rest of your body.

“By causing a change to your brain chemistry, antidepressants may lift your mood. However, antidepressants don't work for everyone, and there is no scientific evidence that depression is caused by a chemical imbalance which is corrected by antidepressants.”

It is also possible that some antidepressants may disrupt pain signals in the brain, leading to the relief of long-term pain.

Format and Brands

Antidepressants are available as tablets, capsules, liquids and drops, although most people take them as tablets.

The same antidepressant may have several different brand names. For example, fluoxetine is sold under a variety of brand names including Olena, Oxactin, Prozac and Prozep.

Dosage

According to NHS Choices (2015),

“When prescribing antidepressants, your GP usually selects the lowest possible dose thought necessary to improve your symptoms.

“This approach is intended to reduce the risk of side effects. If this dose doesn't work, it can be gradually increased.

“Antidepressants are usually taken in tablet form. Depending on the type of antidepressant prescribed and the severity of your depression, you'll usually have to take one to three tablets a day.”

For the latest information on specific formulations and recommended dosages please see our website entries on specific antidepressants or refer to the BNF (British National Formulary).

Usage

If antidepressant medication is prescribed, you should start with a low dose, use the minimum effective dose needed and regularly review the benefits and any adverse events.
 
When choosing antidepressant medication, you should take into account any side effects, the costs, your preference, and your response to any previous treatment with an antidepressant.

In general the newer SSRIs and SNRIs should be chosen over the older MAOIs and tricyclics because they are safer and produce less severe side effects. 

Cost and Time

Cost

In the UK antidepressants are available free of charge to patients within the NHS. In other countries the costs may be covered by some insurance policies.

For the latest information on costs please see BNF (British National Formulary) and BNF for Children.

Time

According to the NHS Choices (2015),

“Antidepressants usually need to be taken for around seven days (without missing a dose) before the benefit is felt. It's important not to stop taking them if you get some mild side effects early on, as these effects usually wear off quickly.

“If you take an antidepressant for four weeks without feeling any benefit, speak to your GP or mental health specialist. They may recommend increasing your dose or trying an alternative medication.

“A course of treatment usually lasts for six months, although a two-year course may be recommended for people with a previous history of depression. Some people with recurrent depression may be advised to take them indefinitely. “

NHS Choices (2015), also notes

“You shouldn't suddenly stop taking antidepressants, even if you feel better. Stopping suddenly can lead to withdrawal symptoms, such as:

  • stomach upsets
  • flu-like symptoms
  • anxiety
  • dizziness
  • sensations in the body that feel like electric shocks
  • seizures (fits)

“Coming off antidepressants too soon can cause your condition to return, and stopping before you have been taking them for three to four weeks may mean the medication hasn't had a chance to take effect.

“If your GP or mental health specialist decides to stop your course of antidepressants, they'll reduce the dose gradually over a few weeks.”

Risks and Safety

Hazards

According to Mind (2016), there are some side effects that are common to all antidepressants of a particular type.

“Side effects that all drugs of this type can cause (most common first)

“SSRIs and SNRIs      

  • decreased alertness
  • sexual problems
  • diabetes
  • SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
  • serotonin syndrome
  • suicidal feelings
  • neuroleptic malignant syndrome
  • hypomania or mania

“Tricyclic and tricyclic-related antidepressants

  • antimuscarinic effects
  • tooth decay
  • decreased alertness
  • suicidal feelings
  • serotonin syndrome
  • SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
  • diabetes
  • neuroleptic malignant syndrome
  • hypomania or mania

MAOIs           

  • decreased alertness
  • SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
  • serotonin syndrome
  • diabetes
  • suicidal feelings
  • neuroleptic malignant syndrome
Autism

There is some evidence that some specific antidepressants may be potentially harmful to people on the autism spectrum. For example, according to NICE (2013),

“There was single study evidence for statistically significant harms associated with the antidepressant citalopram, including: increased energy level; disinhibited, impulsive or intrusive behaviour; decreased attention and concentration; hyperactivity; stereotypy; diarrhoea; any insomnia and initial insomnia or difficulty falling asleep; skin or subcutaneous tissue disorder.”

Contraindications

Some antidepressants may be contraindicated (something which makes a particular treatment or procedure potentially inadvisable) in certain groups of people or under certain circumstances.  For example, according to NHS Choices (2015)

  • Antidepressants can react unpredictably with other medications, including over-the-counter medications such as ibuprofen
  • You should never take two different types of antidepressants, such as an SSRI and a TCA, unless advised by the doctor in charge of your care. This is because taking certain combinations of antidepressants can make you feel very ill and can be life-threatening
  • As a precaution, antidepressants aren't usually recommended for most pregnant women, especially during the early stages of a pregnancy.
  • As a precaution, the use of antidepressants if you're breastfeeding isn't usually recommended.
  • The use of antidepressants isn't usually recommended in children and young people under the age of 18. This is because there's evidence that, in rare cases, they can trigger thoughts about suicide and acts of self-harm in this age group.
  • You should be wary of drinking alcohol if you're taking antidepressants, as alcohol is itself a depressant and drinking alcohol can make your symptoms worse.
  • The use of illegal drugs isn't recommended if you're taking antidepressants, particularly if you've been prescribed a TCA. This is because they can cause unpredictable and unpleasant effects
  • Taking St John's Wort with other medications, such as ... antidepressants ..., can also cause serious health problems.
  • Some antidepressants can cause dizziness, drowsiness and blurred vision, particularly when you first start taking them. If you do experience these problems, you should avoid driving or using tools and machinery.

According to the Royal College of Psychiatrists (2015), there are also some specific contraindications for certain types of antidepressants. For example,

  • SSRIs: There is some evidence of increased suicidal thoughts (although not actual suicidal acts) and other side-effects in young people taking SSRIs.
  • SNRIs: Venlafaxine should not be used if you have a serious heart problem. It can also increase blood pressure, so this may need to be monitored.
  • Tricyclics: Tricyclics may cause confusion, slowness in starting and stopping when passing water, faintness through low blood pressure, and falls – especially in older people.  If you have heart trouble, it may be best not to take one of this group of antidepressants.
  • MAOIs. MAOIs can give you a dangerously high blood pressure if you eat foods containing a substance called tyramine. If you agree to take an MAOI antidepressant your doctor will give you a list of foods to avoid.

Explanation of terms

Antimuscarinic (type of drug used to treat gastrointestinal problems); diabetes (condition caused by excessive glucose); hypomania or mania (over active and excited behaviour); neuroleptic malignant syndrome (life threatening condition resulting from use of some drugs); Serotonin syndrome (symptoms resulting from use of drugs which change levels of serotonin); Syndrome of Inappropriate Antidiuretic Hormone Secretion (unnecessary production of the antidiuretic hormone); tyramine (natural compound found in some foods).

More information

There are numerous publications and websites which provide more details on the potential hazards and contraindications for antidepressants including Mind (2016); NHS Choices (2015), Royal College of Psychiatrists (2015).

Suppliers and Availability

Suppliers

In the UK antidepressants are available free of charge to patients within the NHS.

Credentials

According to the NHS Choices (2015),

“Many antidepressants can be prescribed by your GP, but some types can only be used under the supervision of a mental health professional.”

History

The oldest types of antidepressants (MAOIs and tricyclics) were developed in the 1950s and 1960s.  The next types of antidepressants (SSRIs, SNRIs and NASSAs) were developed in the 1980s and 1990s.

The first antidepressant was isoniazid, an MAOI, which was actually designed as a treatment for tuberculosis. However it was accidentally found to have euphoric effects on patients, some of whom showed increased vigour and appetite, weight gain, improved sleep, and sociability. This discovery led to the development of a range of other MAOI antidepressants including isocarboxazid, phenelzine and tranylcypramine.

The next group of antidepressants to be discovered accidentally were tricyclics, drugs that were actually designed to work as antihistamines.  The first tricyclic antidepressant was imipramine which was followed by a range of other tricyclics including amitriptyline, desipramine and trimipramine.

The comparable effects of MAOIs and tricyclics led researchers to suggest that these drugs shared a common mode of action, that is, they both led to an increased availability of serotonin in the brain.

The first SSRI was zimeldine, a drug specifically designed to increase the production of serotonin within the brain. It was soon followed by other SSRIs including citalopram, fluoxetine and sertraline.  

The first SNRIs, were venlafaxine and duloxetine, drugs specifically designed to block the absorption of serotonin within the brain. The first NASSA was mirtazapine, a drug specifically designed to block the absorption of noradrenaline and serotonin in the brain.

Current Research

We carried out a systematic search for research reviews, and clinical guidance, on the topic of antidepressants as a treatment for people on the autism spectrum in September 2016. 

We identified numerous peer-reviewed scientific reviews on the topic of medications for autism but only four of these looked specifically at antidepressants. Of these, one review (Hurwitz et al, 2012) looked only at tricyclic and tricyclic-like antidepressants and three reviews (Posey et al, 2006; West et al, 2009; Williams et al, 2013) looked only at selective serotonin reuptake inhibitors (SSRIs).

We were unable to find any reviews or studies which looked only at monoamine oxidase inhibitors (MAOIs), only at serotonin-noradrenaline reuptake inhibitors (SNRIs) or only at noradrenaline and specific serotonergic antidepressants (NASSAs).

We also examined the clinical guidance published by The National Institute of Health and Care Excellence (NICE) and other organisations.

According to the National Institute of Health and Care Excellence (2013), which looked at a range of antidepressants

“There was .... no evidence for a significant positive treatment effect of antidepressant drugs on overall autistic behaviours. However, there was evidence for a number of significant adverse events associated with antidepressants.”

“Using [our] expert knowledge and opinion, [we] concluded that antidepressants should not be used to target core features of autism in children and young people.”

According to Hurwitz et al (2012), who looked at tricylics

“A limited sample of TCAs have shown small positive effects in children and adolescents with ASD, but the strength of this evidence is negatively impacted upon by the inconsistent findings between studies, the small sample sizes of the studies and their unclear risk of bias, making clear recommendations impossible at this time.”

“Clinicians considering the use of TCAs in ASD need to be aware of the limited and conflicting evidence of effect and the side effect profile of TCAs when discussing this treatment option with patients with ASD and their carers. More research is required before TCAs can be recommended for use in ASD”

According to Williams et al. (2013), who looked at SSRIs

“There is no evidence that selective serotonin reuptake inhibitors (SSRIs) are effective as a treatment for children with autism. In fact, there is emerging evidence that they are not effective and can cause harm.

“For adults, small positive effects have been seen with fewer side effects reported with fluoxetine and fluvoxamine, but the possible risk of bias and small sample size of the trials mean there is not strong evidence to support these treatments. A small study of citalopram in adults with high levels of repetitive behaviours has shown no positive effects.”

“Decisions about the use of SSRIs for established clinical indications that may co-occur with autism, such as obsessive-compulsive disorder and depression, and anxiety (in the case of adults), should be made on a case-by-case basis.”

According to West et al (2009), who looked at SSRIs

“This review suggests that SSRIs are somewhat effective in treating overall autism severity and disruptive and repetitive symptoms, but treatment is often accompanied by side effects. Autistic children seem to have increased side effects to minimal doses of medication when compared to normally developing peers. The most frequently cited side effects of SSRI treatment include behavioral activation (hyperactivity and agitation), aggression, and suicidal ideation.”

“The lack of controlled, randomized double-blind studies of the majority of serotonin modulating drugs severely restricts the ability to draw conclusions about efficacy and safety of SSRIs for children with autism. Most of the studies retrieved were open-label observational studies or retrospective chart reviews and case reports of small cohorts of patients from a single clinical facility. Such studies provide valuable exploratory information but have inherent limitations.

According to Posey et al (2006), who looked at SSRIs

 “To date, placebo controlled studies of SSRIs have involved only fluvoxamine (in children and adults) and fluoxetine (in children). Open-label and retrospective studies of all other SSRIs in PDDs have also been published that suggest effectiveness. Despite these positive reports, there continues to be questions about the tolerability and appropriate dosing of SSRIs in children with PDDs. Because of the limited number of placebo-controlled studies, definitive conclusions about the role SSRIs should play in the clinical treatment of children with PDDs cannot be drawn.”

Future Research

Summary of Existing Research

There is insufficient high quality research evidence to determine if antidepressants have any effect on the core features of autism, such as restricted, repetitive patterns of behaviour, interests, or activities.

There is insufficient high quality research evidence to determine if antidepressants have any effect on mental health problems, such as depression and anxiety, in people on the autism spectrum.

There is insufficient high quality research evidence to determine if antidepressants have any effect on other issues, such as challenging behaviours, in people on the autism spectrum.

There is evidence of significant side effects of some antidepressants in some people, including in some individuals on the autism spectrum. Those side effects may include decreased alertness, sexual problems, diabetes, SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion), serotonin syndrome, suicidal feelings, neuroleptic malignant syndrome and hypomania or mania.

Recommendations for Future Research

Future research should

  • determine which antidepressants are effective for the treatment of which issues in which individuals on the autism spectrum
  • compare antidepressants with other, non-medicinal interventions designed to tackle depression, anxiety and other issues in people on the autism spectrum
  • investigate the optimal dosage and length of treatment for different individuals, while also investigating any long-term effects.

Studies and Trials

You can find details of studies and trials into specific antidepressants in our publications database 

Updated
31 Oct 2017
Last Review
01 Jan 2017
Next Review
01 Jan 2020