Category: Depression

Ketamine for depression could be effective in 40 minutes and last for weeks, although safety issues remain.

Ketamine — sometimes known as a ‘horse tranquiliser’ or club drug — is not a new drug, although its use for those with depression is relatively new.

Recent studies have found that it can lift depression in as little as 40 minutes and treat people for a week or longer.

The fact that ketamine for depression works so quickly, and on one of the most resistant forms of depression, has many researchers fascinated.

Traditional antidepressants can be slow to work — if they work at all.

The problem with using ketamine as a treatment for depression is that it gives people an addictive high.

Similar drugs to ketamine, though, without the side-effects, which act on the same chemical pathways, are also being developed.

These could provide hope for those who suffer some of the most debilitating types of depression.

How ketamine for depression treatment works

Research has provided a critical insight into how ketamine works — and possibly a way to side-step its addictive properties  (Zanos et al., 2016).

Scientists at the National Institutes of Health (NIH) have found that it is not the ketamine itself that causes the antidepressant effect.

Instead, it is another substance into which ketamine is broken down by the body that provides the effect (a metabolite).

Dr Carlos Zarate, one of the study’s co-authors, said:

“This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works and holds promise for development of more robust and safer treatments.

By using a team approach, researchers were able to reverse-engineer ketamine’s workings from the clinic to the lab to pinpoint what makes it so unique.”

Although previous research has been carried out on humans, the new study tested ketamine for depression in mice.

It found that the mechanism of action was not what many had assumed.

Instead it works through a glutamate receptor: α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)

With this information the scientists were able to make an antidepressant which worked on the mice without the side-effects.

Dr  Todd Gould, one of the study’s authors, said:

“Now that we know that ketamine’s antidepressant actions in mice are due to a metabolite, not ketamine itself, the next steps are to confirm that it works similarly in humans, and determine if it can lead to improved therapeutics for patients.”

70 percent respond to ketamine for depression

Fully 70 percent of people in one study who were given the drug responded to it — despite previously not improving with other standard depression treatments (Tiger et al., 2020).

Ketamine increases the brain’s production of dopamine.

Dopamine is involved in how we process rewards: when we eat delicious foods, help others, exercise and fall in love, the brain produces dopamine.

One of the key symptoms of depression is finding it difficult to seek out and experience rewards — people feel there is nothing to look forward to.

Dr Mikael Tiger, the study’s first author, said:

“In this, the largest PET study of its kind in the world, we wanted to look at not only the magnitude of the effect but also if ketamine acts via serotonin 1B receptors.

We and another research team were previously able to show a low density of serotonin 1B receptors in the brains of people with depression.”

The study included 30 people with depression that had not responded to other treatments.

They were given either a dose of ketamine for depression or a placebo.

Brain scans revealed that ketamine operates through serotonin 1B receptors.

The effect is to reduce the release of serotonin, but increase the release of another neurotransmitter called dopamine.

Dopamine is part of the brain’s reward system, which helps to attract people to positive experiences.

Those who wished to continue, received ketamine for a further two weeks, twice a week.

The results showed that over 70 percent responded to the treatment.

Dr Johan Lundberg, study co-author, said:

“We show for the first time that ketamine treatment increases the number of serotonin 1B receptors.

Ketamine has the advantage of being very rapid-acting, but at the same time it is a narcotic-classed drug that can lead to addiction. So it’ll be interesting to examine in future studies if this receptor can be a target for new, effective drugs that don’t have the adverse effects of ketamine.”

Esketamine for depression as a nasal spray

Researchers have been examining different ways to administer ketamine and in different forms.

A nasal spray containing a form of ketamine for depression — a type of anaesthetic — can help severely depressed and suicidal people, research finds (Canuso et al., 2018).

The form of ketamine works quickly, and on one of the most resistant forms of depression.

When people are severely depressed there is a critical window when they need rapid relief from suicidal thoughts.

While antidepressants can be beneficial in the long-run, they cannot help people when they are at highest risk because they take too long to kick in.

The study tested a nasal spray containing esketamine — a part of the ketamine molecule — on 68 people experiencing severe depression and suicidal thoughts.

Half received treatment as normal plus a placebo and the other half received treatment as normal plus the nasal spray.

The results showed that the nasal spray was effective in rapidly reducing suicidal feelings within 40 minutes of being administered.

The effects were still being seen after 24 hours, in comparison to those receiving a placebo.

The more esketamine people were given, the longer its effect.

The drug has now been approved by the FDA in the US.

The problem with using ketamine as a treatment for depression is that it gives people an addictive high, so safety issues will need to be explored.

The study’s authors conclude:

“These preliminary findings indicate that intranasal esketamine compared with placebo, given in addition to comprehensive standard-of-care treatment, may result in significantly rapid improvement in depressive symptoms, including some measures of suicidal ideation, among depressed patients at imminent risk for suicide.”

Ketamine treatment for bipolar disorder

Ketamine and similar drugs are also being tested for the relief of other mental health problems.

One example is bipolar disorder.

When depressed, bipolar patients find it difficult to seek out and experience rewards — they feel there is nothing to look forward to.

Ketamine works by changing how people think about rewards, a study finds  (Lally et al., 2014).

Dr. Carlos Zarate, who led the study, said:

“Our findings help to deconstruct what has traditionally been lumped together as depression.

We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants — and link that response to different circuitry than other depression symptoms.”

In the study, 36 patients with bipolar disorder who were currently depressed were given either ketamine or a placebo.

They were then asked about their depression and symptoms of anhedonia, the inability to experience pleasure.

The first effect of the drug was to reduce patients’ anhedonia within 40 minutes: they could once again anticipate and experience pleasure.

After two hours, the drugs anti-depressant effects were also felt.

This reduction in anhedonia was still detectable two weeks after the single dose.

Brain scans revealed that the drug likely works by changing the way the motivational parts of the brain respond to imagining and taking part in pleasurable experiences.

.

People eating this way are less likely to suffer from depression and other mental health problems.

People who eat intuitively have a lower chance of developing mental health problems, research finds.

Eating intuitively means eating based on hunger and fullness.

Dieting or restricting food intake is the opposite of intuitive eating.

Everyone is probably an intuitive eater when they are born.

But, over the years, the effects of social conditioning change how some people view food.

People learn that wasting food is bad, that certain tasty foods should be avoided, along with a host of other rules.

Unfortunately, these rules can paradoxically make people desire the banned foods more.

Some end up eating to excess because of the restrictions they have placed on themselves.

The conclusions come from a study of 1,491 adolescents who were tracked over 8 years, between the ages of around 14 to 22.

They were all asked questions like:

• do you stop eating when you are full?
• do you trust your body to tell you how much to eat?
• do you eat everything on your plate, even when no longer hungry?

The idea was to see whether the young people were trusting their own internal bodily states or following some external guidelines.

The results showed that intuitive eaters tend to trust their own body so they stop when they are full, rather than when the plate is empty.

Intuitive eaters, it emerged, experienced fewer depressive symptoms, more satisfaction with their body, higher self-esteem, less binge eating and fewer extreme or unhealthy weight control behaviours.

People with the intuitive food behaviours were 74 percent less likely to binge eat.

Dr Vivienne Hazzard, the study’s first author, said:

“The fact that these results came from such a diverse sample suggests that the benefits of intuitive eating seem to cut across racial, ethnic, and socioeconomic lines.”

The study was published in the Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity (Hazzard et al., 2020).

Common types of depression have been categorised in many ways, but the forms are resistant to structure.

Depression is a very complex state which is why the signs and types of depression are wide-ranging and often confusing.

Depression is certainly much more than just feeling sad.

Because of the complexity of depression, scientists are not sure exactly how many ‘types’ there are — or even if it can be comprehensively put into types.

Psychiatrists and psychologists use a series of categories that have emerged over the years, which seem to describe some people’s experience of depression, but are highly unsatisfactory.

Major depression

Major depression is relatively common and can last weeks or months and may have no clearly identifiable cause.

Symptoms can include:

• sadness,
• changes in appetite,
• lack of concentration,
• memory problems,
• thoughts of death
• and feelings of worthlessness.

Major depression is also sometimes called major depressive disorder, clinical depression, melancholic, psychotic or many other names.

Briefly, here are some of the types of depression that are commonly referred to:

1. Bipolar disorder: What used to be called manic depression. Its most obvious symptom is very severe mood swings; it is a condition of extreme emotional states.
2. Persistent depression: lasting two or more years.
3. Psychotic depression: includes periods of delusions and hallucinations.
4. Perinatal depression: related to pregnancy and childbirth.
5. Seasonal depression: brought on by seasonal changes.
6. Situational depression: reacting to the death of a loved one, a divorce or other tragedy.
7. Atypical depression: depression that does not fit into the other categories.

New approaches to types of depression

The system of types of depression outlined above has grown up over the years in a disorganised manner.

Some modern attempts have been made to put depression into categories that are more comprehensive.

Here are three of those typologies:

There are 4 types of depression

One recent attempt is through the use of brain scans (Drysdale et al., 2016).

The brain scans revealed distinctly different types of brain activity in each sub-type.

Dr. Conor Liston, who led the research, said:

“The four subtypes of depression that we discovered vary in terms of their clinical symptoms but, more importantly, they differ in their responses to treatment.

We can now predict with high accuracy whether or not a patient will respond to transcranial magnetic stimulation therapy, which is significant because it takes five weeks to know if this type of treatment works.”

The four different types of depression they identified are:

• Biotype 1 is characterised by anxiety, insomnia, and fatigue.
• Biotype 2 is characterised by exhaustion and low energy.
• Biotype 3 is characterised by an inability to feel pleasure as well as slowed movements and speech.
• Biotype 4 is characterised mostly by anxiety with insomnia along with the inability to feel pleasure.

They are called ‘biotypes’ because of the biological means (brain scans) used to identify them.

Previously, symptoms have been used to identify different types of depression.

But this can produce unsatisfying answers.

It is hoped that a biological approach will help to provide some extra precision for diagnosis and treatment.

Dr Liston said:

“Depression is typically diagnosed based on things that we are experiencing, but as in election polling, the results you get depend a lot on the way you ask the question.

Brain scans are objective.”

The conclusions come from a study of over 1,100 fMRI brain scans of people with depression, compared with healthy controls.

Researchers at seven different institutions worked to identify the abnormal patterns of connectivity in the brains and how they were linked to depressive symptoms.

They found the patterns clustered together.

For example, one group had reduced connectivity in the part of the brain that is important for fear-related behaviour.

This was most often seen in sub-types 1 and 4, both of which are characterised by high levels of anxiety.

Dr Liston concluded:

“Subtyping is a major problem in psychiatry.

It’s not just an issue for depression, and it would be really valuable to have objective biological tests that can help diagnose subtypes of other mental illnesses, such as psychotic disorders, autism and substance abuse syndromes.”

There are 12 types of depression

Another analysis of types of depression argues that depression is actually formed of 12 different sub-types, many of which have very different causes (Rantala et al., 2017).

Mr Severi Luoto, study co-author, said:

“The evidence that major depressive disorder is a group of separate syndromes comes from the observations that patients not only have many hundreds of unique symptom profiles, but many of the symptoms often have opposite features such as insomnia or hypersomnia, or an increase or decrease in appetite.”

These 12 sub-types of depression are set off by:

1. Infection, in which sickness behaviour to combat pathogens and parasites may lead to symptoms such as loss of appetite, sleep disturbances, anhedonia, impaired concentration.
2. Long-term stress which is known to activate the immune system, causing an increase in proinflammatory cytokine levels that influence mood.
3. Loneliness.
4. Traumatic experience.
5. Hierarchy conflict where events such as unemployment, exclusion from a social group, bullying at school or professional hierarchy conflicts may trigger a depressive episode.
6. Grief.
7. Romantic rejection.
8. Postpartum events which lead to depression in 10-15% of women.
9. The season, where Seasonal Affective Disorder (SAD) affects the individual at the same time each year.
10. Chemicals such as alcohol and cocaine.
11. Somatic diseases such as Alzheimer’s, Parkinson’s, migraine, epilepsy, stroke and traumatic brain injury.
12. Starvation which is known to reduce mood and, when prolonged, can lead to apathy and social withdrawal.

Professor Markus Rantala, the study’s first author, said:

“With the help of the 12 depression subtypes, it will be easier to find more effective treatments for depression.

This is because the focus will be on treating the underlying reasons (triggers) of depression instead of merely focusing on the symptoms, which is how traditional psychiatry treats depression.

We argue that the occurrence of symptoms (or patterns of symptoms) depends on the subtype of the depressive episode.

The particular manifestation of depressive symptoms may have more to do with what triggered the depression (i.e. the proximate mechanisms) than the personality of the patient.”

Diagnosing people using these sub-types should make treatments more effective.

There are 5 types of depression

People who are depressed often also feel anxious, so some researchers have tried to incorporate both depression and anxiety into their description of types.

Instead of being ‘depressed’ and/or ‘anxious’, some research suggests five different types of depression and anxiety (Grisanzio et al., 2017).

The five are tension, anxious arousal, general anxiety, anhedonia — the inability to feel pleasure — and melancholia.

Each type has its own particular symptoms and effects on the brain.

The researchers describe the types as follows:

1. Tension

This type is defined by irritability.

People are overly sensitive, touchy, and overwhelmed.

The anxiety makes the nervous system hypersensitive.

2. Anxious arousal

Cognitive functioning, such as the ability to concentrate and control thoughts, is impaired.

Physical symptoms include a racing heart, sweating, and feeling stressed.

Professor Leanne Williams, who led the study, explained:

“People say things like ‘I feel like I’m losing my mind.

They can’t remember from one moment to the next.”

3. Melancholia

People experience problems with social functioning.

Restricted social interactions cause further distress.

4. Anhedonia

The primary symptom is an inability to feel pleasure.

This type of depression often goes unrecognized.

People are often able to function reasonably well while in a high state of distress.

Professor Williams said:

“We see it in how the brain functions in overdrive.

People are able to power through but at some time become quite numb.

These are some of the most distressed people.”

5. General anxiety

A generalized type of anxiety with the primary features involving worry and anxious arousal—a more physical type of stress.

Overlapping symptoms

Psychologists typically find that anxiety and depression share many overlapping symptoms.

The five categories arrived at in this study come from over 800 people, some of whom had anxiety and depression diagnoses.

They had complete psychiatric testing, along with analysis of their outlook on life, their social relationships and their functioning in everyday life.

The patterns of brain activation and symptoms suggested five categories.

The study found that the most common type was the ‘tension’ type.

Ms Katherine Grisanzio, the study’s first author, said:

“Interestingly, we found that many people who did not meet diagnostic criteria, but were still experiencing some symptoms, fell into the tension type.”

After this, anxious arousal was the next most common type, then melancholia and general anxiety, while the least common type was anhedonia, the inability to feel pleasure.

Currently, anxiety and depression are treated in much the same way, Professor Leanne Williams, who led the study, said:

“…the treatments would be the same for anyone in these broad categories.

By refining the diagnosis, better treatment options could be prescribed, specifically for that type of anxiety or depression.”

.