Category Archives: Mental health

Guidelines for the Management of Bipolar Disorder.

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turner

The first German-language guidelines for the management of bipolar disorder were published in 2012, and now, an abbreviated English translation is available online for free [link].

The German Society for Bipolar Disorder (DGBS) and the German Association for Psychiatry & Psychotherapy (DGPPN) set up a project group, a steering group and 6 working groups made up of psychiatrists, psychotherapists, patients and their families. Devoid of any industry funding, their intention was to provide “decision-making support for patients, their families, and therapists“. Following an extensive literature review, and ten consensus conferences they concluded:

“Bipolar disorder should be diagnosed as early as possible. The most extensive evidence is available for pharmacological monotherapy; there is little evidence for combination therapy, which is nonetheless commonly given. The appropriate treatment may include long-term maintenance treatment, if indicated. The treatment of mania should begin with one of the recommended mood stabilizers or antipsychotic drugs; the number needed to treat (NNT) is 3 to 13 for three weeks of treatment with lithium or atypical antipsychotic drugs. The treatment of bipolar depression should begin with quetiapine (NNT = 5 to 7 for eight weeks of treatment), unless the patient is already under mood-stabilizing treatment that can be optimized. Further options in the treatment of bipolar depression are the recommended mood stabilizers, atypical antipsychotic drugs, and antidepressants. For maintenance treatment, lithium should be used preferentially (NNT = 14 for 12 months of treatment and 3 for 24 months of treatment), although other mood stabilizers or atypical antipsychotic drugs can be given as well. Psychotherapy (in addition to any pharmacological treatment) is recommended with the main goals of long-term stabilization, prevention of new episodes, and management of suicidality. In view of the current mental health care situation in Germany and the findings of studies from other countries, it is clear that there is a need for prompt access to need-based, complex and multimodal care structures. Patients and their families need to be adequately informed and should participate in psychiatric decision-making“.

The abridged guidelines (in English) are available here.

 

Baclofen & Topiramate for Alcohol Dependence?

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wine bottles

A new paper appraises promising strategies for the treatment of drug addiction in general. The authors consider agents which target GABA transmission, ion-channels and the emerging technique of repetitive transcranial magnetic stimulation (rTMS). In their elegant review of the field, perhaps the most noteworthy findings involve the treatment of alcohol dependence with either baclofen or topiramate.

Baclofen

Baclofen is a GABA-b agonist, which has been used in neurology for years. Several open-label studies, and 2 out of 3 randomised controlled trials (RCTs) have suggested that baclofen is effective in alcohol dependence by reducing cravings and promoting abstinence. Baclofen is safe (even in subjects with liver cirrhosis) and is generally well tolerated with sedation being the most notable side-effect. Higher doses of baclofen appear to be more effective, but this needs confirmation in further RCTs.

Topiramate

Topiramate enhances inhibitory and dampens excitatory currents in neurons, and has been used as an anticonvulsant for years. In 2 relatively large RCTs, topiramate was effective in alcohol dependence, by reducing cravings and the severity of dependence, and improving physical and psychosocial outcomes. Topiramate is generally well tolerated, although cognitive side effects can occur, and it should be avoided in pregnancy.

The full paper can be read here.

Dopamine & psychosis: Old fashions, new findings.

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Dopamine is the archetypal late '60s, early '70s transmitter, famous for it's involvement in schizophrenia. Like much else from this era, the dopamine story is discovered anew by successive generations. That story – that the dramatic symptoms of schizophrenia are caused by too much dopamine – has survived as fashions have come and gone.

dopamine terminal

Dopamine is synthesised in pre-synaptic boutons from the amino-acid tyrosine (TYR), via DOPA. Patients who respond well to anti-psychotics appear to have increased synthesis of dopamine (DA).

A recent paper from researchers in London adds a new twist. It appears that those patients who respond well to anti-psychotic drugs (which block dopamine receptors) have elevated pre-synaptic dopamine. In contrast, the (thankfully small) group of patients who don't do so well on anti-psychotics appear to be no different from healthy controls in regard to pre-synaptic dopamine.

Further work, including replication of the findings, will be necessary. But these results suggest that there are dopamine and non-dopamine forms of psychosis.

Hopefully, in time, there will be technological improvements allowing prospective testing of individual patients prior to initiating drug therapy. New, non-dopamine based anti-psychotics are also a priority.

The abstract can be read here

Download a free high-res vector graphic.

Cool Memories: The Recurring Crisis of Psychiatry.

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The diagnostic system for delineating psychiatric disorders ('The DSM') is in it's fifth rewrite. It had been anticipated that advances in fMRI imaging and molecular genetics would have finally put psychiatric diagnoses on a medical footing. Alas fMRI has failed to live up to it's promise. And genetics, if anything, has been too powerful – by toppling the whole framework of DSM.

A new paper by Juan & Maria-Ines Lopez-Ibor captures the zeitgeist, but also reveals that the current debates and controversies are nothing new. For over 150 years, psychiatry/psychology has struggled to establish itself as a natural science because of three major issues – 1. Classification difficulties. 2. The mind-brain duality problem. 3. The perils of phrenology (localisationism).

[The full paper can be read here].

These issues have been acknowledged many times before, but never as a collective – and perhaps never as elegantly (even with some minor errors of translation from Spanish into English).

On classification…

“Psychopathological phenomena certainly exist and can be observed and experienced as such. However, psychiatric diagnoses are arbitrarily defined and do not exist in the same sense as psychopathological phenomena do”.

On dualism…

“Dualism manifests itself in the separation of mental and physical diseases, of psychiatry and the rest of medicine, of neuroses and psychosis, of biological research and interventions from other psychosocial approaches and in the proliferation of psychiatric sub-disciplines”.

& on phrenology (localisationism)…

“A phrenological approach still survives in neurological and psychiatric research…This approach has been extended to the neuropharmacology attributing specific neurotransmitters psychological functions”.

The text may be gloomy, for some. Others may engage in playful delight at references to Plato, Greisinger and the Upanishads. A follow up paper is in press (this was part 1), and much is promised…

“Modern science and modern medicine are, no doubt, the greatest achievements of humankind having change for the better of millions of human beings. We are not arguing to throw the baby with the water in the tub, but to look for fresh water to replace or replenish the existing one. This we will do in the second part of this article”.

 

NMDA receptor encephalitis: An acute organic psychosis.

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Mental health clinicians should be mindful that numerous physical illnesses can present with psychiatric symptoms. A case in point is a recently described autoimmune disorder in which antibodies target glutamate NMDA receptors within the brain. Acute psychosis and cognitive dysfunction are so prominent in this condition, Anti-NMDA receptor encephalitis, that many patients are initially referred to psychiatry. Swift and accurate diagnosis is essential, as the appropriate therapy is immunological rather than psychiatric.

The antibody targets the extra-cellular portion of the NMDA receptor. Initially, there is an increase of NMDA mediated currents. But hypofunction emerges, the receptor appears to be internalised and vital functions such as long-term potentiation (LTP), which are essential for cognition, are lost. [see link]

Anti-NMDA receptor encephalitis

Symptoms and signs

Anti-NMDA receptor encephalitis was first described in young women with underlying ovarian tumours. But cases in males, in children and non-tumour cases are well documented. In about 20% of presentations, neuropsychiatric symptoms are preceded by a flu-like illness. Early symptoms in adults are psychosis (hallucinations, delusions and bizarre behaviour), cognitive impairment (confusion, memory dysfunction, dysphasia), and seizures. Over days to weeks additional neuropsychiatric features emerge; movement disorder (choreoathetoid, myoclonus, parkinsonism, rigidity), autonomic instability (tachy/bradycardia, labile BP, hypersalivation, central hypoventilation) and reduced levels of consciousness [full paper].

Investigations

In terms of investigation, CSF lymphocytosis, CSF oligoclonal bands, EEG slowing and epileptiform potentials can be found. The MRI scan is usually normal. The diagnosis is clinched by the presence of CSF IgG antibodies against the NR1 subunit of the NMDA receptor.

Treatment

The treatment of choice is immunotherapy (IV steroids, IV immunoglobulin, plasma exchange) – as well as tumour resection. A good outcome is associated with a decrease in NMDA receptor antibody levels. In some patients the recovery is prolonged, and 2nd line immunotherapies are required. Interestingly, many patients have also responded well to modified ECT.

NMDA receptor autoantibodies & Schizophrenia?

There has been recent interest in the possibility that many cases of diagnosed schizophrenia may actually be alternative forms of anti-NMDA receptor encephalitis. But the evidence for this is not convincing. In a Spanish study of 80 patients, no cases were positive for anti-NMDA receptor IgG antibodies. In a larger study from Germany (approx 450 acute patients), there was an excess of anti-NMDA receptor antibodies in acute schizophrenia (10%) versus major depression (3%). But these were not the IgG antibodies against the NR1 subunit, which is the defining feature of NMDA receptor encephalitis. Instead there were IgA and IgM antibodies against the NR1 and NR2 subunits. The significance of these antibodies is not entirely clear, especially as they were also found in healthy controls (0.4%). Are they a marker of a prior insult against the NMDA receptor or an incidental finding? – A question which will now attract much research.