Question:
I consider ECT very inhumane and I am willing to try anything to find an alternative solution. We have seen so called best psychiatrists in India and they have not been able to help us. Now we would like to try elsewhere (possibly US) and I will be really grateful if someone can suggest a good hospital/doctor for psychotic depression. And also let me know if it is possible to control severe depression without ECT.
Answer:
I want to get answer for some of my questions regarding
medication for psychotic depression that has made my father's life
miserable.
My father is 61 years old and he suffers from psychotic depression
from past 9 years. Once it was diagnosed in 1992, he was put on
anti-depressants and it worked for few years, later he was given
ECT (electro convulsive therapy) whenever he entered severe depression.
This would happen once/twice a year. But his condition deteriorated
gradually and now he is on a maintenance ETC of once a month!
The doctors say it is a very rare case of severe unipolar depression
and so far they have not been able to find an alternative to ECT.
I consider ECT very inhuman and I am willing to try anything to
find an alternative solution. we have seen so called best psychiatrists
in India and they have not been able to help us.
Now we would like to try elsewhere (possibly US) and I will be really
grateful if someone can suggest a good hospital/doctor for psychotic
depression. And also let me know if it is possible to control severe
depression without ECT.
The National Foundation for Depressive Illness, Inc. maintains "800" lines which, presently
through a recorded message, provide callers with the symptoms of depression and manic
depression and inform them of how to receive a packet of additional information from NAFDI.
This additional information includes a referral list, by state, of doctors and support groups as
well as a bibliography, our brochure and additional relevant articles. The number to call,
toll-free, is 1-800-245-4306.
If you are familiar with the symptoms of depression and manic depression and prefer not to
listen to the recording, you may write to us, The National Foundation for Depressive Illness,
Inc. (or NAFDI) at Post Office Box 2257, New York, NY 10116-2257 and request the
information. Please enclose a self-addressed envelope of business size or larger with $0.97 of
U.S. postage affixed (for U.S. addresses). As we are a not-for-profit organization, if you can
afford it, please enclose a contribution of $5 or more. If you can't afford that, please let us
know and we'll be happy to send you exactly the same material at no charge.
You may also visit us at our web page .
A major goal of antidepressant development is to improve on preceding
drug classes with agents with greater specificity (and therefore fewer
unwanted side-effects) and with more rapid onset of antidepressant
action. To this end, four antidepressants with significantly distinct
pharmacological characteristics have been recently introduced:
venlafaxine, nefazodone, mirtazapine, and reboxetine. Venlafaxine is the
first antidepressant in a new drug class referred to as the serotonin
noradrenergic reuptake inhibitors (SNaRIs). Nefazodone is a weaker
serotonin and norepinephrine reuptake inhibitor, but a potent serotonin
5-HT2 receptor antagonist. Mirtazapine is a potent antagonist of central
2alpha-adrenergic autoreceptors, and heteroreceptors and is an
antagonist of serotonin 5-HT2 and 5-HT3 receptors. The result of these
actions is to increase both noradrenergic and specific (5-HT1)
serotonergic transmission, and mirtazapine has therefore been termed a
noradrenergic and specific serotonergic antidepressant (NaSSA).
Reboxetine is the first selective noradrenaline reuptake inhibitor
(NaRI) to be introduced since the tricyclics, and lacks immediate
serotonergic effects.
Select any of the following topics after going to this site:
http://www.biopsychiatry.com/new.htm
TCAs
SSRIs
NARIs
RIMAs
Options
SSRIs/SNRIs
21st century
Sigma ligands
Plato v Aristotle
Antidepressants
New antidepressants
Future pharmacotherapies
The monoamine hypothesis
From:
http://www.gwdg.de/~bbandel/gjp-article-keppel-hesselink2.htm At the recent European Congress for Neuropsychopharmacology (ENCP), held
in Paris in November 1998, much information was shared about the
atypical neuroleptics, a reason to review this class of drugs.
Chlorpromazine, the first phenothiazine neuroleptic, began the
revolution in the treatment of schizophrenia in the early 1950s.
However, this drug has many troublesome side effects, limiting its use.
Haloperidol, the next step in treating schizophrenia has since its
introduction been used to treat millions of patients of all ages over
nearly 4 decades.
The launch of clozapine on the world market in 1990 led to the
establishment of a new group of neuroleptics that for the time being are
referred to as the atypical neuroleptics.
Atypical neuroleptics are all said to be able to reduce positive and
negative symptoms of schizophrenia, without inducing EPS, for which
enough proof exists (1). These drugs have generally been found to be
more effective than conventional antipsychotics against the totality of
negative symptoms. The usefulness of the typical neuroleptics in the
treatment of the negative symptoms of schizophrenia has always been a
weak point of these agents.
Atypicality has been ascribed to 5-HT2/D2 antagonism, although the exact
pharmacological mechanism underlying the efficacy of the atypical
neuroleptics is not yet known. Furthermore, they have serotonin,
adrenergic, histamine, and acetylcholine receptor blockade effects that
may be involved with the antipsychotic effect (2).
Since the introduction of clozapine, a drug with a ten-fold higher
affinity for D4 compared to D2 or D3 receptors and the gold standard in
treating neuroleptic-refractory schizophrenic patients, a large number
of new atypical neuroleptics have been tested and introduced into
clinical use or are about to be launched: risperidone, olanzapine,
zotepine, ziprasidone, sertindole and quetiapine. Many other compounds
are still in the early clinical pipeline: LU 111995, a D4 and 5HT2A
antagonist (phase IIa) and BTS 79018, a D3 and 5HT1A agonist, M100907, a
selective 5-HT2A receptor antagonist, and novel benzothiazepine
derivatives with affinity for 5-HT2, D2, and D3 receptors (preclinical
phase), to mention only a few.
Recent data on the degree of dissociation at the D2 receptor show that
antipsychotic drugs which induce parkinsonism (trifluperazine,
chlorpromazine, haloperidol, fluphenazine) bind more strongly than
dopamine to D2, while those antipsychotic drugs which elicit little or
no parkinsonism (melperone, quetiazepine, clozapine, sulpiride,
olanzapine, sertindole) bind more loosely than dopamine to D2 receptors
(3)
There is further evidence that some of the atypical neuroleptic activity
might be due to H3 autoreceptor antagonism, thus increasing the
histamine levels in the brain (4).
The atypical neuroleptics can also be of use to treat violent behaviour.
This occurs in nearly 13% of schizophrenic patients, and occurs often in
the context of positive psychotic symptoms (i.e., delusions or
hallucinations)(5). A common side effect of all atypical neuroleptics is
weight gain, and dependent on the compound can be up to 4 kg (6).
Various atypical agents, such as olanzapine, risperidone, and
sertindole, seem to cause tardive dyskinesias, but at a much lower rate
than haldol (1% vs. 5%). Only clozapine does not seem to cause any TD.
Zotepine (Knoll)
Zotepine, a tricyclic compound, structurally similar to clozapine, was
presented at the recent ECNP by Knoll scientists as a broad spectrum
antipsychotic drug with high affinity for D1 and D2 receptors, as well
as for 5HT2, 5HT6 and 5HT7 receptors (7). A unique feature of this drug
was claimed to be its NA-reuptake inhibition in the nanomolar range,
which could have clinical relevance for the treatment of comorbid
affective states. Zotepine elevates dopamine in the frontal cortex of
rats, as measured by the microdialysis method (8). Zotepine, clozapine
as well as haloperidol were reported to elevate enkephaline mRNA levels
in the limbic area, a property suggested to be relevant to its
neuroleptic activity (9). In 3 double-blind, placebo controlled trials,
a dose range between 75 and 450 mg was tested against haloperidol and
chlorpromazine. Cooper presented data of a recurrence prevention study
in 121 patients, treated with 50-100 mg tid. The risk of recurrence over
a 25-week period was significantly reduced in the patients treated with
zotepine. Somnolence and weight gain were the most frequent side
effects. Specific details on dose-finding, side effect profile and data
of the individual trials were not presented. An intramuscular
formulation and a liquid formulation are under development. Market
launch in Germany and Austria is expected in November, according to a
spokesperson of Knoll.
Olanzapine (Lilly) and Risperidone (Janssen)
Risperidone and olanzapine were the first 2 new atypical neuroleptics
introduced on the market. It is clear that this is one of the reasons
why the first direct comparative trials testing these two compounds are
now being reported. Some of these direct comparisons were presented at
the ECNP, but the details of the methodology used in these trials was
not released. Thus, a final judgement on whether one of these compounds
is superior to the other is still outstanding. However, the overall
efficacy will most probably be comparable. It may be that one or other
compound will have certain advantages for a certain type of patient.
Olanzapine has a broad receptor profile similar to that of clozapine. It
is as effective as haloperidol against the positive symptoms of
schizophrenia, and more effective against negative symptoms, with
significantly fewer extrapyramidal side effects. Side effects include
somnolence and weight gain. New data on the efficacy and safety were
presented of trials comparing risperidone and olanzapine.
During a Lilly-sponsored symposium Stuart Montgomery (UK) presented
preliminary data from a double-blind, placebo-controlled, international
trial in over 300 patients were olanzapine (10-20 mg) was compared to
risperidone (4-12 mg). He presented the PANSS depression scores:
olanzapine was superior to risperidone.
Some anecdotal data were presented based on case studies suggesting that
one could use risperidone to boost the efficacy in partially refractory
patients treated with olanzapine or clozapine (10). ...I am very sorry to hear that your father is so very ill
and must undergo unsuccessful treatment. I am not sure
where you should go or a doctor. I am just writing to
tell you that there may be alternatives or somewhere where
you can write to get more specific information for
your father's case.
I found this site which may answer some of your questions:
http://www.mentalhealth.com/book/p45-dp01.html
Also take a look at this page:
http://www.mentalhealth.com/p.html
where you may click on contacts and other links for
help.
