Safety warning: Hydroxyzine

Source: EMA

PRAC recommends new measures to minimise known heart risks of hydroxyzine-containing medicines Medicines can still be given for their approved uses, with new restrictions EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has completed a review of medicines containing the antihistamine hydroxyzine. This follows concerns over the risk of possible effects on heart rhythm with these medicines, which are available in most EU countries. Their approved uses (indications) vary considerably between countries and may include use to treat anxiety disorders, for relief of pruritus (itching), as premedication before surgery, and for treatment of sleep disorders. The PRAC considered that hydroxyzine was associated with a small but definite risk of QT interval prolongation and torsade de pointes (alterations in the electrical activity of the heart that can lead to abnormal heart rhythms and cardiac arrest). Based on the assessed data, the risk did not differ between indications, and the Committee recommended that hydroxyzine could continue to be used provided that measures to minimise the risk of problems with heart rhythm were taken. These measures include using the medicine at the lowest effective dose for as short a time as possible. Use is not recommended in the elderly. The maximum daily dose should be no more than 100 mg in adults (50 mg in the elderly if use cannot be avoided), and 2 mg per kg body weight where used in children up to 40 kg in weight. Use must be avoided in patients who already have risk factors for heart rhythm disturbances or are taking other medicines that increase the risk of QT prolongation. Care is also needed in patients taking medicines that slow the heart rate or decrease the level of potassium in the blood, as these also increase the risk of problems with heart rhythm. The PRAC recommendation follows a detailed review of the available evidence, which included published studies and data from regular safety monitoring, as well as consultation with experts in the treatment of children and the elderly. PRAC confirmed the known possibility of QT interval prolongation and torsade de pointes with hydroxyzine, and noted that such events were most likely to occur in patients who had risk factors. The risk can therefore be decreased by restricting hydroxyzine use in those most at risk of heart rhythm problems and reducing exposure to the medicine. The Committee recommended further study and monitoring to ensure that these measures were effective. The product information should be updated accordingly. The PRAC recommendation will now be forwarded to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a final position and provide guidance to patients and healthcare professionals. In the interim, patients who have any concerns should consult their doctor or pharmacist.

Inflammation is a big player in early psychosis


It has long been known that inflammtory processes play some part in psychosis, be it schizophrenia, depression, or mania.

The results of the above mentioned study again corroborate this finding.

Future therapeutic intervention may very well be aimed at controlling the inflammatory process associated with psychosis (although the usual caveat of „further studies are needed certainly apply).

A diet enriched with Curcumin might help against anxiety and PTSD


Curcumin, a yellow-pigment compound found in the popular Indian spice turmeric (Curcuma longa), has been extensively investigated for its anti-inflammatory, chemopreventative, and antidepressant properties. Here, we examined the efficacy of dietary curcumin at impairing the consolidation and reconsolidation of a Pavlovian fear memory, a widely studied animal model of traumatic memory formation in posttraumatic stress disorder (PTSD). We show that a diet enriched with 1.5% curcumin prevents the training-related elevation in the expression of the immediate early genes (IEGs) Arc/Arg3.1 and Egr-1 in the lateral amygdala (LA) and impairs the ‘consolidation’ of an auditory Pavlovian fear memory; short-term memory (STM) is intact, whereas long-term memory (LTM) is significantly impaired. Next, we show that dietary curcumin impairs the ‘reconsolidation’ of a recently formed auditory Pavlovian fear memory; fear memory retrieval (reactivation) and postreactivation (PR)-STM are intact, whereas PR-LTM is significantly impaired. Additional experiments revealed that dietary curcumin is also effective at impairing the reconsolidation of an older, well-consolidated fear memory. Furthermore, we observed that fear memories that fail to reconsolidate under the influence of dietary curcumin are impaired in an enduring manner; unlike extinguished fear memories, they are not subject to reinstatement or renewal. Collectively, our findings indicate that a diet enriched with curcumin is capable of impairing fear memory consolidation and reconsolidation processes, findings that may have important clinical implications for the treatment of disorders such as PTSD that are characterized by unusually strong and persistently reactivated fear memories.

Oxytocin Facilitates the Extinction of Conditioned Fear in Humans


Biological Psychiatry 10/2014; DOI: 10.1016/j.biopsych.2014.10.015


Current neurocircuitry models of anxiety disorders posit a lack of inhibitory tone in the amygdala during acquisition of Pavlovian fear responses and deficient encoding of extinction responses in amygdala–medial prefrontal cortex circuits. Competition between these two responses often results in a return of fear, limiting control over anxiety. However, one hypothesis holds that a pharmacologic strategy aimed at reducing amygdala activity while simultaneously augmenting medial prefrontal cortex function could facilitate the extinction of conditioned fear.


Key among the endogenous inhibitors of amygdala activity in response to social fear signals is the hypothalamic peptide oxytocin. To address the question whether oxytocin can strengthen Pavlovian extinction beyond its role in controlling social fear, we conducted a functional magnetic resonance imaging experiment with 62 healthy male participants in a randomized, double-blind, parallel-group, placebo-controlled design. Specifically, subjects were exposed to a Pavlovian fear conditioning paradigm before receiving an intranasal dose (24 IU) of synthetic oxytocin or placebo.


Oxytocin, when administered intranasally after Pavlovian fear conditioning, was found to increase electrodermal responses and prefrontal cortex signals to conditioned fear in the early phase of extinction and to enhance the decline of skin conductance responses in the late phase of extinction. Oxytocin also evoked an unspecific inhibition of amygdalar responses in both phases.


Collectively, our findings identify oxytocin as a differentially acting modulator of neural hubs involved in Pavlovian extinction. This specific profile of oxytocin action may open up new avenues for enhancing extinction-based therapies for anxiety disorders.

Golden rain tree extract better than nicotine patches!



Extract of golden rain tree proved to be better than nicotine patches for help to quit smoking.
This might be a totally new approach….and it’s apparentyl also cheaper. (see link)

Controversy: Mobile Apps That Deliver Advice and Therapy..?

Can your smartphone replace your therapist?

There are quite a number of apps for both iPhone and Android that claim to be helpful for certain conditions, includind psychiatric symptoms….

The evidence, however, is lacking in many cases and some apps may actually be harmful.


Read the article here:

Nitrous oxide against therapy resistant depression?

Well, it seems to work in this pilot study‘

20 therapy resistant depressed patients were given inhalations of nitrous oxide or placebo – and the group given nitrous oxide showed improvement on depression scores.

Nitrous oxide, like ketamine, works as an NMDA receptor antagonist. This could be their shared mechanism of action in depression.

Now the result has to be confirmed in a larger group.

No such thing as schizophrenia. But many.


Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies

Recent findings corroborate what „we all“  know: There is no such thing as schizophrenia. That said: There are many forms of schizophrenia!
This research points towards the existance of at leastz 8 subtypes, each with different gtenetic background, each with different symptoms and prognosis. However, using the currently accepted diangnostic criteria, all these conditions would be classified as „schizophrenia“.
The subtypes have a different clinical course and outcome, and they might also respond to different treatment.
This finding is important because it points out that, possibly, we have grouped different patients into the same category and subejcted them to not only the same diagnosis and prognosis, but also to the same treatment. Actually, things might be a little bit more complicated. Biological psychatry at least (comprising genetics, chemistry, pharmacology etc.) seems to suggest this possiblity.

Glutamate-receptor autoantibodies in Schizophrenia


JAMA Psychiatry. 2013 Mar;70(3):271-8. doi: 10.1001/2013.jamapsychiatry.86.

Increased prevalence of diverse N-methyl-D-aspartate glutamate receptor antibodies in patients with an initial diagnosis of schizophrenia: specific relevance of IgG NR1a antibodies for distinction from N-methyl-D-aspartate glutamate receptor encephalitis.

Autoantibodies angainst glutamate receptors are found in a high percentage of patients diagnosed with schizoprenia, especially in first diagnoses. They could contribute or even cause many symptoms in at least a part of all schizophrenia cases. Hoewever,  it is currently not common practice yet, to assess the presence of those antibodies in all first diagnosis cases of schizophrenia.

New service: Get a text message appointment reminder


We offer a new service: Text message reminders for your appointment one or two days prior to the scheduled date. Please tell me if you want to receive a reminder per text message.
This service is provided free of any costs for you. However, the service is still in „beta-phase“, so I cannot guarantee it works every time.

Moritz Muehlbacher MD