Tag Archives: treatment

Major mental illness and the Love hormone

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Oxytocin for schizophrenia – More positive news

Oxytocin is a hypothalamic peptide which is involved in social cognition and social behaviour. It is sometimes colloquially referred to as the 'love hormone', given it's involvement in bonding, empathy and trust. In recent years, oxytocin has been proposed as a possible new treatment for psychiatric disorders in which inter-personal relationships are problematic. The list of candidate conditions has included social anxiety disorder, autism and schizophrenia.

In the case of schizophrenia, clinical trials have begun to appear in the last few years. Two American groups have reported promising findings in small-scale studies. New findings from a trial carried out by researchers based in Tehran are also positive. The Iranian trial has the advantage in that patients were followed up for 8 weeks, compared to 2-3 weeks in the US studies. It was also slightly larger in size.

In the Iranian study, the addition of oxytocin to risperidone led to improvements in the intensity of positive psychotic symptoms (hallucinations, delusions and suspiciousness). There were also improvements in negative symptoms (apathy, amotivation, reduced sociability), although this was less pronounced.

The authors concluded: “Oxytocin as an adjunct to risperidone tolerably and efficaciously improves positive symptoms of schizophrenia. In addition, effects on negative and total psychopathology scores were statistically significant, but likely to be clinically insignificant. The interesting findings from the present pilot study need further replication in a larger population of patients.“

The paper is available here

 

Complementary Treatments for Depression

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Exercise, meditation and nutritional supplements in depression: Helpful or not?

Since 1965 it has been clear from clinical trials that antidepressant medications are effective in major depression. However many patients are not keen to take tablets, expressing a wish for more 'natural' forms of treatment. Numerous alternative treatments have been advocated, but is there any evidence that any of these work? Here we briefly review the case for physical exercise, meditation (or mindfulness, as it is now known) and several nutritional supplements.

Alternative treatments as a group can often be criticised because they do not subject themselves to rigorous trials, as is the case with conventional treatments (pharmacological or psychological). This criticism is valid. Indeed it is only within the last 60 years that conventional medicine itself has demanded clear demonstrations of efficacy before a treatment can be licensed for a particular illness. The randomised, double-blind control trial (RCT) is the gold standard by which efficacy is judged. Until recently, very few alternative treatments were subjected to the strict demands of the RCT. But this is changing.

Is physical exercise beneficial in depression?

There is now good evidence that a programme of physical exercise is an effective treatment for depression. Researchers in Brazil conducted a metanalysis in which the results from 10 separate trials were pooled to give an overall finding. (Metanalysis is a powerful method for deciding whether a treatment works. All available trials are scrutinised, and those with no control group or no randomised allocation to drug or placebo are usually excluded on the grounds of being poor quality studies).

stretching exercisesThe main finding from the Brazilian study was that moderate exercise (3 times per week) was effective in reducing depressive symptoms. Those patients who were older, and those with milder depression derived the most benefit. It made no difference whether the exercise programme involved strength-training or aerobic training, although the authors showed a preference for aerobic training. The authors concluded:

“The present meta-analysis concluded that physical exercise, mainly aerobic training, improves the response to depression treatment. However, the efficacy of exercise in the treatment of depression was influenced by age and severity of symptoms“.

The full paper can be read here.

Meditation (Mindfulness)

Mindfulness is a currently fashionable psychological approach for the treatment of depression, which has its roots in eastern meditation techniques. The various traditional schools of meditation differ in flavour, but all centre on the idea of mastering an unruly and restless mind. Mindfulness training involves short sessions in which the aim is to direct consciousness towards full immersion in the activity at hand, rather than on the mind's incessant chatter. But does it work?

meditation candle

A recent review from the US attempted to tackle this question. However the authors were unable to reach a definitive conclusion. At present there are not enough studies, of sufficient quality, to yield an answer. They point out that further (and more robust) trials are needed, but they regard mindfulness as a promising approach to depression. They remark:

“Regardless of the various limitations present in the available literature, findings to date have consistently demonstrated that training focused on improving attention, awareness, acceptance, and compassion may facilitate more flexible and adaptive responses to stress“.

The full paper can be read here.

Nutritional Supplements

Vitamin deficiencies (especially B-vitamins) can cause neuropsychiatric disorders, although this is very rarely seen now in developed countries. But the idea of supplementation is to provide additional quantities of a specific nutrient in an effort to obtain a therapeutic effect. Three nutrients in particular have attracted attention as possible treatments for depression: folic acid, S-adenosylmethionine (SAM-e) and omega-3 fatty acids. A recent Canadian paper has reviewed the evidence.

nutritional supplements

Omega-3 fatty acids (fish oils) have been shown to possess antidepressant properties in a metanalysis of 16 trials. SAM-e has also been shown to be effective in a metanalysis of 7 trials. The evidence in support of folic acid has been more limited. One of two trials was positive and further work is needed. The authors conclude:

“Physicians should consider screening for and treating folate deficiency but the benefits of folate supplementation remain unclear. Limited evidence supports the use of omega-3 fatty acids and S-adenosylmethionine, but further research is required“.

The full paper can be read here

 

 

New treatments for schizophrenia?

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The 1st generation anti-psychotics

It is sometimes said that all the treatments in psychiatry were discovered by chance (or serendipity, to use the technical term), rather than by planning. This is not strictly true. In fact many of our treatments for schizophrenia were discovered by design. The rationale was to start with a molecule which could induce a transient psychosis, even in healthy people – a molecule like amphetamine or LSD.

Thereafter the task was to find a drug which could block the effects of the psychosis-inducing compound. Such a drug, it was reasoned, could be an effective medicine for schizophrenia.

A Belgian researcher called Paul Janssen used this approach to great effect. He observed the effects of amphetamine in professional cyclists, who were using the drug to combat fatigue. Many of the cyclists developed an acute psychosis which was identical to paranoid schizophrenia. Janssen was the owner of a private research facility and was in an ideal position to search for medicines which could block amphetamine.

Progress was rapid and the compound haloperidol was discovered. And it turned out that haloperidol was a highly effective medicine for schizophrenic psychoses. Used in small doses, without interruption, haloperidol is a powerful treatment against hallucinations, delusions and agitation. But high doses are best avoided, as they can cause movement disorder.

The 2nd generation anti-psychotics

With this success of haloperidol, attention focused on other psychosis inducing drugs. This time LSD was taken as the psychosis-inducing agent. Numerous reports had shown that LSD (or 'acid') could transform consciousness in a way which was similar to the experience of people with schizophrenia. What was needed was a compound to block LSD, followed by a trial of the new compound in people with schizophrenia. Again the approach worked, giving us the medicine risperidone.

Olanzapine, sertindole, quetiapine and others followed. This class of anti-psychotic has become the first-line treatment in many countries and carries much less propensity to cause movement disorder as a side effect. However, careful attention is needed to avoid problems of weight gain and high cholesterol. Haloperidol acts on the dopamine system whereas second generation anti-psychotics like risperidone work on dopamine, but also target another brain transmitter called serotonin.

The next generation anti-psychotics

Two other drugs of abuse are associated with psychotic reactions. The first of these is ketamine, which has become popular on the club scene. Ketamine can elicit bizarre changes in consciousness which resemble the picture of schizophrenic psychosis. Ketamine can also induce the so-called negative symptoms. (Apathy, loss of drive and a reduced capacity for emotions, along with a rigid, concrete style of thinking).

The glutamate NMDA channel. Ketamine blocks the channel. Drugs which counteract ketamine may be useful antipsychotic medicines.

 

Ketamine works on the glutamate signalling system. As before the task was to find a compound which blocked the effects of ketamine. This has now been done, and in fact there are several different types of molecule available (Bitopertin, AMG747).

Now the challenge is to assess if any of these new compounds are good treatments for schizophrenia. At this time, several clinical trials in schizophrenic patients are underway, including some at The Institute of Psychiatry in London.

The other promising lead involves compounds which can block the effects of cannabis. About a dozen recent studies have shown that repeated use of cannabis is a risk factor for the development of schizophrenia. Skunk cannabis is known to be particularly hazardous for mental health. (Skunk contains high THC).

THC acts at cannabinoid receptors. Drugs which block the effects of THC are showing promise as medicines for schizophrenia.

 

Our research group and others have shown that a natural molecule called CBD can oppose the effects of THC in humans. CBD therefore becomes a candidate anti-psychotic medicine. Already one trial in Germany has found CBD to be as effective as a second generation anti-psychotic in people with schizophrenia. A number of larger studies are now underway. For an svg image click here.

 

Summary

There is an ongoing search for new medicines in schizophrenia. The first compounds such as haloperidol led to a fundamental change in psychiatric practice. The second generation medicines 'solved' the problem of motor side-effects, but at the cost of obesity and other metabolic complications. Hopefully a new generation of effective anti-psychotics will emerge in the next few years. Like their predecessors, the roots of their development may well be in design rather than by chance.

 

New insights into how antidepressants work.

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fMRI scan.

It is well established that antidepressants take at least 2 weeks to shift a depressed mood. A new study from researchers at Oxford, reveals that the drug is working behind the scenes, much earlier than this.

People with depression are known to show an exaggerated response to pictures of human faces that are expressing fear. The response can be observed using functional MRI brain scanning. The part of the brain which lights up is their own 'fear processor', the amygdala. The usual interpretation is that the depressed patient's fear system is unduly sensitive to anything from the outside world which signifies fear. And human faces elicit the most robust response.

Previous work had shown that standard SSRI antidepressants can dampen down the hyperactive amygdala, and return it's function to normal. What was unknown was whether the effect on the amygdala or the effect on mood came first.

The Oxford researchers have now shown that SSRI antidepressants dampen down the amygdala at least 1 week before the patient experiences a shift in their mood. They compared 3 groups of people: depressed patients who had been randomised to receive escitalopram (10mg); depressed patients who had been randomised to placebo; and a group of healthy controls. A week after being randomised to active drug or placebo, the depressed patients were given an fMRI scan.

The main finding was that the patients who had been taking escitalopram for a week had normal amygdala responses to pictures of fearful human faces. In contrast, the patients on placebo showed the characteristic hyperactive response in the amygdala on the right hand-side of their brains (see scan above). Notably, 1 week was too early for any antidepressant effect – Treated and untreated patients were equally depressed at this stage.

This is an important finding, which shows that SSRI antidepressants affect how the brain processes emotional information before the patient feels an improvement in their mood.

Further studies are planned. One key goal will be to assess if the degree of amygdala dampening at 1 week can distinguish between patients who ultimately get better from those who will remain depressed. The technology might even be used in selecting the 'best' type of antidepressant drug for a particular patient, rather than having to adopt a 'wait and see' approach.

The full paper can be read here

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488813/

 

N-acetylcysteine: Effective in bipolar depression?

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N-acetylcysteine (NAC) is a derivative of the naturally occurring amino-acid cysteine. Many people use it as a nutritional supplement, but NAC also has clear pharmacological properties. By far the most important role of NAC is as an ‘antidote’ in cases of paracetamol overdose. In this role, it can be life-saving.

However, the properties of NAC may extend beyond the emergency room. Recent research from Australia suggests it might be effective in the depressive phase of bipolar disorder. http://www.scielo.br/pdf/rbp/v33n4/v33n4a11.pdf

Larger studies are needed, but if the initial promise holds true, this would represent an important advance. In bipolar disorder, the depressive phase can be extremely difficult to shift, although conventional pharmacology has also made some significant inroads in the past few years. http://journals.psychiatryonline.org/data/Journals/AJP/4013/1351.pdf