# Stopped taking antipsychotic



## cipher (Jan 25, 2011)

My psychiatrist asked me to stop taking Amisulpride ( antipsychotic ) which was prescribed by a neurologist who earlier diagnosed me with pseudoneurotic schizophrenia. My Psychiatrist says it is not schizophrenia. Even I feel the same.

I am on Sertraline 100 mg..


----------



## Visual (Oct 13, 2010)

cipher said:


> My psychiatrist asked me to stop taking Amisulpride ( antipsychotic ) which was prescribed by a neurologist who earlier diagnosed me with pseudoneurotic schizophrenia. My Psychiatrist says it is not schizophrenia. Even I feel the same.
> 
> I am on Sertraline 100 mg..


Was the Amisulpride making your problems worse? (How was it affecting you?)


----------



## cipher (Jan 25, 2011)

Visual Dude said:


> Was the Amisulpride making your problems worse? (How was it affecting you?)


I stopped taking amisulpride bcoz my psychiatrist and I think that it was a wrong diagnosis ( pseudoneurotic Schizophrenia by the *other* neurologist) , also I was having muscle twitching more than usual..


----------



## Visual (Oct 13, 2010)

cipher said:


> I stopped taking amisulpride bcoz my psychiatrist and I think that it was a wrong diagnosis ( pseudoneurotic Schizophrenia by the *other* neurologist) , also I was having muscle twitching more than usual..


So aside from the twitching, it didn't seem to affect you either good or bad?

But the Sertraline is helping, how does it make you feel?


----------



## cipher (Jan 25, 2011)

Visual Dude said:


> So aside from the twitching, it didn't seem to affect you either good or bad?
> 
> But the Sertraline is helping, how does it make you feel?


It was neutral.. I guess it helped me like 10 % .. I have been taking sertraline besides amisulpride.. So I can't actually say that I benefited from Amisulpride or sertraline..


----------



## 35467 (Dec 31, 2010)

Amisulpride or Solian is a dopaminic stimulant in a low dose -below 200.mg and a blocker in of dopamine in higher doses. The low dose is used to treat "negative symptoms" within schizophrenia disorders- such as anhedonia. Its stimulates dopamine in a low dose by blocking the dopaminic pre-synatic autoreptors witch is 7- times more sensitive the post-synaptic. A blocking of a pre synaptic autoreceptor makes more dopamine. Dopamine plays a role indircly in DP by not in the pathway affected by amisulpride.


----------



## Visual (Oct 13, 2010)

Mayer-Gross said:


> Amisulpride or Solian is a dopaminic stimulant in a low dose -below 200.mg and a blocker in of dopamine in higher doses. The low dose is used to treat "negative symptoms" within schizophrenia disorders- such as anhedonia. Its stimulates dopamine in a low dose by blocking the dopaminic pre-synatic autoreptors witch is 7- times more sensitive the post-synaptic. A blocking of a pre synaptic autoreceptor makes more dopamine. Dopamine plays a role indircly in DP by not in the pathway affected by amisulpride.


*Dopamine plays a role indircly in DP by not in the pathway affected by amisulpride.*

Would like to learn more specifically about this. Would you elaborate?


----------



## 35467 (Dec 31, 2010)

It is thougt that symptoms of DP is made by an stimulation of the kappa opiopid receptor. There is an interaction between the kappa and dopaminic system so that when kappa is overactive dopamine goes down. In 2. recent studies in people with major depression and DP/DR and just Major depression it was found in the DP/DR group a significant rise in the hormone prolactin. There is a relationship between low dopamine and high prolactin and vise versa. Prolactin cells can not be active in the presence of dopamine. The studies didn´t relate to the kappa receptor but studies in human and amimals have shown that drugs that stimulate kappa gives a rise in prolactin and drugs like naloxone and namefene can block this. By the way many with DP suffers from migranes and floters -these 2. symtoms could be related to a higher prolactin level and reflecting a low dopamine level in the part of the brain connected to the kappa system.


----------



## 35467 (Dec 31, 2010)

As I wrote - kappa actity lowers dopamic tone in this pathway ; mesolimbic-mesocortical and nigrostriatal dopaminergic systems. It is currently belived the kappaopiopid receptor is prime suspect in DP.

http://www.ncbi.nlm.nih.gov/pubmed/9862779

http://www.ncbi.nlm.nih.gov/pubmed/18593955

http://www.ncbi.nlm.nih.gov/pubmed/8105790


----------



## Visual (Oct 13, 2010)

Mayer-Gross said:


> As I wrote - kappa actity lowers dopamic tone in this pathway ; mesolimbic-mesocortical and nigrostriatal dopaminergic systems. It is currently belived the kappaopiopid receptor is prime suspect in DP.
> 
> http://www.ncbi.nlm.nih.gov/pubmed/9862779
> 
> ...


Thank you for the info.

These articles seem to focus more on dysphoria and delusion - do you think that DP/DR may be a form/state of these?

*It is currently belived the kappaopiopid receptor is prime suspect in DP*

Would you supply more info about this?


----------



## 35467 (Dec 31, 2010)

M. Sierra mentetions that in his book. The reason that trails with Naltraxone and naloxone works and are problematic in DP is these drug low affinity for the kappa receptor and high for mu receptor. That you need doses 10-times normal to take dp symptoms indicate kappa. Two other trails with a kappa agonist in normal made symptoms of DP - in one of the studies this effect was blocked by 10.mg of naloxone.In 2008 I wrote to M.Sierra regarding a drug called nalmefene with can block kappa in normal dose and i was wandering why it havn´t been tried.He wrote that a trail with nalmefene had been considered but didn´t come of. He agreed with me that there was a milage with nalmefene. He wrote in his book that cannabinole blockers could be an future option because cannabis can trick DP. I send him some notes that proved that cannabis also is a partiel agonist on the kappa receptor and it poited twards the opiopate system not away in regard to cannabis. A ´nother thing scans with a fMRI of DP points to a hypoperfusion of structure called insula cortex -the place which gives sense of self and agency.

Nalmefene in oral form will come on the market in the coming year http://www.lundbeck.com/investor/pipeline/development_programs/default.asp

Effect of naloxone therapy on depersonalization: a pilot study

Yuri L. Nuller, Marina G. Morozova, Olga N. Kushnir and Nikita Hamper
Bekhterev Psychoneurological Research Institute. St-Petersburg, Russia.

To test the hypothesis of the role for the opioid system in the pathogenesis of depersonalization, the effect of naloxone (an opioid receptor blocker) on the symptoms and corticosteroids secretion was studied in patients with depersonalization syndrome. Fourteen depersonalization patients were treated with naloxone: 11 patients received single doses (1.6 or 4 mg i.v.) and three others received multiple infusions, with the maximal dosage being 10 mg, and the effect of naloxone on symptom severity was determined. In eight patients, the cortisol, cortisone and corticosterone content in the blood plasma was determined prior to and after the 4 mg naloxone infusion. A reversed-phase microcolumn high-performance liquid chromatography with ultraviolet detection was applied for assessment of glucocorticoids. In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization.

Introduction
Depersonalization is a change of self-awareness such that the
person feels unreal. It is characterized by the loss of emotional
perception or a blunted feeling of one's own body and its functions,
etc. Patients with this condition find it difficult to describe, often
speaking of being detached from their own experience and unable
to feel emotion. A similar change in relation to the environment is
called derealization. Depersonalization can manifest itself as a
symptom in the structure of various psychopathological syndromes
or as an independent syndrome. In the latter case, where the
depersonalization syndrome is unrelated to any other mental
disease, it is defined as a depersonalization disorder (Nuller, 1982;
American Psychiatry Association, 1994).
Depersonalization syndrome often has a long, lingering course
which is resistant to therapy (Shader, 1994). Antidepressants,
neuroleptics and electroconvulsive therapy usually fail to produce
any therapeutic action. Only very large doses of benzodiazepines
produce a therapeutic effect in some patients (Nuller, 1982; Gelder
et al., 1989). In cases where depersonalization lasts for months and
years, no psychotropic therapy has documented efficacy. When
depersonalization is a part of another mental disorder, it is most
often a major depression. In such cases, depression can become
resistant to therapy and have a lingering course.
An effective medical treatment of depersonalization is impaired
by the lack of data on the biochemical mechanisms of this disorder.
Depersonalization usually develops as a reaction to severe
emotional stress, or can emerge from acute anxiety and tension in
various mental illnesses. The fact that anxiety is involved in its
genesis is confirmed by the therapeutic efficacy of large doses of
anxiolytics in the acute depersonalization syndrome (Nuller, 1982;
Nuller and Mickalenko, 1988). Stress can be accompanied by
secretion of endogeneous opioids, mostly beta-endorphins. This
helps to explain the hypoalgesia or total analgesia found in
depersonalization (Nuller and Mikhalenko, 1988; Moroz et al.,
1990; Abugova, 1996) as well as a less pronounced pupil reaction
to morphine (Nuller and Mikhalenko, 1988). These observations
led us to suggest that disturbance in the opioid system such as the
increased endorphin secretion and/or a change in the sensitivity of
opioid receptors play an important role in the pathogenesis of
depersonalization. To verify this hypothesis, we investigated the
effect of naloxone - an opioid receptor blocker. Stress is also
characterized by changes in secretion of corticoids. Therefore it
was of interest to determine the levels of corticoids under
depersonalization.

Methods/Subjects

Fourteen patients (nine females and five males, mean age 32 years)
were assigned to treatment with naloxone. In six patients,
depersonalization was the only manifestation of a mental illness
and they met the DSM-IV criteria for depersonalization disorder.
Eight patients had mixed depersonalization and depressive
symptoms with dominating depersonalization syndrome. In three
patients, the duration of the disease was less than 1 year, in seven
patients, it ranged from 1-5 years; in two patients, from 5-10 years
and in two patients, 14 and 16 years.
The control group for plasma corticosteroids included 36 healthy
volunteers whose age ranged from 25-45 years and whose
corticosteroid level in the blood plasma was determined twice for
two subsequent days.

Naloxone Administration

Naloxone (Polfa) was injected i.v. at 12 in the afternoon in a
single-blind placebo controlled design, with placebo always first.
The patients had one dose of naloxone, which was followed by
further doses if they did not respond. Eleven patients had one
infusion, the doses were 4 mg in nine patients and 1.6 mg in two
patients. Three patients had multiple naloxone infusion: in one
case, 2 mg infusions within 3 days (6 mg total) and, in two other
cases, multiple infusions with doses increasing from 2 mg to 10 mg
every 2 or 3 weeks (50 mg total). The maximal number of
infusions administered was 10. Between the naloxone infusions,
these two patients received tranquilizers (lorazepam, 6 mg per day;
phenazepam, 8 mg per day; hydroxyzine, 200 mg per day) and
antidepressants (paroxetine, 60 mg per day; mianserine, 90 mg per
day).

Biochemical Methods

The cortisol, cortisone and corticosterone content in the blood
plasma was determined in eight patients prior to and after the
naloxone infusions. Blood was taken from a catheter inserted into
the ulnar vein, and kept open with heparin. The first sample was
taken at 11.00 h immediately after the catheter was inserted; the
second at 11.30 h, after 10 ml of physiological solution (placebo)
was infused iv.; the third at 12.00 h, then the infusion of 0.4 mg of
naloxone (1 ml of naloxone solution and 9 ml of the physiological
solution) was made; the fourth at 12.15 h before the 4 mg naloxone
infusion (10 ml of the solution) and the fifth at 12.30 h.
For measurement of glucocorticoids, a reversed-phase microcolumn
HPLC with ultraviolet (UV) detection was applied. A
150 ´ 1 mm column filled with Separon SGX C18 5μ and linear
gradient elution (70 : 30 to 35 : 65 water-acetonitrile for 30 min)
was used. The technique allowed a good baseline separation of
aldosterone, cortisol, cortisone and corticosterone (Gamper et al.,
1996). The detection limit (UV detection at 254 nm) was
approximately 5 ng/ml. Serum protein electrophoresis was used to
extract the substances of interest from the serum.

Results

Efficacy was assessed using the depersonalization scale (Nuller
and Mikhalenko, 1988) and subjective response. The depersonalization
scale was administered before the naloxone infusion and
after 4 h (peak effect). In three of 14 patients, depersonalization
symptoms disappeared entirely. Seven patients showed a marked
improvement: with symptoms reduced by more than 50% on the
depersonalization scale. One patient showed moderate improvement
and, in two patients, the improvement was short and
insignificant, one patient showed no positive effect.
Thus, 10 of 14 patients showed a considerable therapeutic
effect, which is undoubtedly a success considering the therapeutic
resistance of the depersonalization syndrome. In addition, the
subsequent benzodiazepine therapy (lorazepam, 6 mg per day;
phenazepam, 8 mg per day; hydroxyzine, 200 mg per day within
4 weeks) resulted in a fast and complete reduction of depersonalization
in three patients (two demonstrated considerable and one
moderate improvement), although, in two of these patients, the
same drugs were not effective prior to the naloxone therapy.
After reduction of depersonalization, four patients showed no
evidence of any mental disorder except for the personality traits
they had had in the premorbid period; five patients continued to
express the symptoms of major depressive disorder, which was less
severe than before the depersonalization had manifested itself and
responded quickly to the antidepressants; one patient was found to
be deluded with intense anxiety. This condition showed a good
response to antipsychotic therapy.
In most cases, the first signs of improvement were recorded
soon after the naloxone infusions (within 20-40 min) and the
patients' perception of the world was marked by greater brightness.
A complete reduction or disappearance of depersonalization
occurred within the interval of 1-4 h and, in some patients, continued
for as long as 12-24 h. This was followed by some
deterioration, although the depersonalization never recurred to the
initial level. Five patients showed evidence of a stable improvement.
Two patients had considerable but not total reduction of depersonalization
due to the naloxone therapy. Immediately thereafter,
they received long-term benzodiazepine treatment. The impression
was that benzodiazepines stabilize the improvement that was
reached as a result of the naloxone therapy.
No side-effects were recorded when naloxone was
administered.
Table 1 presents the corticosteroid data. The depersonalization
patients have a very low initial cortisol level compared to the
control. The cortisone level also decreased, but to a smaller degree,
whereas the corticosterone content appeared to be slightly higher.
Upon 4 mg naloxone infusion, the cortisol content was found to
reliably increase compared to its post-placebo level. With respect
to cortisone, it increased but not as drastically and the corticosterone
content remained unchanged.

Table 1 Plasma corticosteroids concentration (ng/ml) in normal controls and depersonalization patients
Cortisol Cortisone Corticosterone
Control group (n = 36)
After catheter insertion 30.5 ± 2.65 22.48 ± 3.24 9.61 ± 1.69
Depersonalization group (n =








After catheter insertion 13.98 ± 0.95*** 16.77 ± 2.54 13.90 ± 2.66
30 min after catheter insertion 11.91 ± 1.36 14.45 ± 2.63 10.45 ± 2.01
15 min after placebo infusion 10.21 ± 1.09 13.84 ± 2.22 9.16 ± 1.10
15 min after naloxone infusion (0.4 mg) 11.53 ± 2.55 15.90 ± 2.56 7.97 ± 1.20
15 min after naloxone infusion (4 mg) 18.64 ± 3.35 20.33 ± 3.17 9.93 ± 2.01

Discussion

Previous attempts to use naloxone for treating mental disorders
proved to be unsuccessful (Abrams et al., 1978; Volavka et al.,
1982; Keuler et al., 1996) and an insignificant positive effect of
short duration was recorded only in case of mania (Janowsky et al.,
1983). The opioid system seems to play an insignificant role in the
pathogenesis of the endogeneous depression (Banki and Araio,
1987). As mentioned above, we used indirect data which suggested
the importance of the opioid system in the pathogeneses of
depersonalization, i.e. some depersonalization symptoms resemble
the effect of morphine and depersonalization arises as a reaction to
an acute emotional stress, which causes endorphin secretion.
The positive therapeutic effect of the opioid receptor blocker,
naloxone, offers some evidence for the implication of the opioid
system in the pathogenesis of depersonalization. This role is also
confirmed by the influence of naloxone on the cortisol secretion in
depersonalization patients: the low level of cortisol in depersonalization
patients could be explained by the fact that endogeneous
opioids inhibit CRF secretion. By blocking the action of
endorphins, naloxone increases the cortisol secretion (Delitala
et al., 1994). The depersonalization patients were found to have
a much lower cortisol content in plasma, which was drastically
increased by naloxone. The increase of cortisol level coincided
in time with the therapeutic effect of naloxone. There was a
reduction of depersonalization symptoms without any signs of
anxiety.
Our data do not provide sufficient evidence to conclude whether
the therapeutic effect of naloxone is only related to the blockade of
the opioid receptors or to some other factors that affect the opioid
system. In most patients, the positive action of naloxone developed
during the first hours after the infusion and, in many, the
improvement lasted more than 24 h. Because the half-life of
naloxone is approximately 60 min, this suggests that naloxone
increased the patients' therapeutic sensitivity to the drugs that were
previously not very effective for these particular patients.
One naloxone infusion was sufficient to entirely eliminate or
considerably reduce all the symptoms of depersonalization in four
patients who had a relatively recent depersonalization syndrome.
However, some symptoms recorded prior to depersonalization
reappeared and were easily treated by conventional medicine. Our
previous data on the positive effect of large doses of benzodiazepines
on depersonalization (Nuller, 1982) are evidence for the
close relationship between depersonalization and anxiety. In most
cases of chronic depersonalization, syndrome reduction was not
accompanied by manifestation of affective symptoms. Here,
depersonalization seems to be unrelated to anxiety and might
become autonomous. The change of sensitivity in opioid receptors
may be important in cases of chronic depersonalization.
In conclusion, some clinical manifestations of depersonalization,
such as analgesia, the suppression of corticosteroid
secretion and especially the positive therapeutic effect of the opioid
receptor blocker, naloxone, offer evidence for the implication of
the opioid system in the pathogenesis of depersonalization.

Address for correspondence
Professor Yuri L. Nuller
The Psychopharmacological Department
Bekhterev Psychoneurological Research Institute
3 Bekhterev St
St-Petersburg 193019
Russia
Email: [email protected]
References
Abrams A, Braff D, Janowsky D S, Holl S, Segal D S (1978)
Unresponsiveness of catatonic symptoms to naloxone.
Pharmakopsychiatry 11: 177-179
Abugova M A (1996) Indices of pain threshold as a method of
objective assessment of depersonalization therapy efficacy.
Bekhterev Rev Psychiatry Med Psychol 4: 120-122
American Psychiatric Association (1994) DSM-lV: diagnostic and
statistical manual of mental disorders, 4th edn. American
Psychiatric Association, Washington DC
Banki C V, Araio M (1987) Multiple hormonal responses to
morphine: relationship to diagnosis and dexamethasone
supression. Psychoendocrinology 12: 3-11
Delitala G, Trainer P S, Oliva O, Fanciully G, Grossman A B (1994)
Opioid peptide and alpha-adrenoreceptor pathways in the
regulation of the pituitary-adrenal axis in man. Endocrinology
141: 163-168
Gamper N L, Velicanova L I, Korolyova N M (1996) Determination
of six corticosteroids in human serum by reversed phase
microcolumn HPLC. Proceedings of the 18th International
Symposium on capillary chromatography V111, pp. 1655-1663
Gelder M, Gath D, Mayou R (1989) Oxford textbook of psychiatry,
2nd edn. Oxford University Press, Oxford
Janowsky D S, Judd L L, Huey L Y, Rish S C, Segal D S (1983)
Behavioral effects of opioid receptor antagonists in
psychopathological states. Psychiatry Clin North Am 6: 403-414
Keuler D J, Altemus M, Michelson D, Greenberg B, Murphy D L
(1996) Behavioral effects of naloxone infusion in
obsessive-compulsive disorder. Biol Psychiatry 40: 154-156
Moroz B T, Nuller Y L, Ustimova I N, Andreev B V (1990) Study of
pain sensitivity based on the indicators of electroodontometry
in patients with depersonalization and depressive disorders.
Zhurnal Nevropatologii Psichiatrii 90: 81-82
Nuller Y L (1982) Depersonalisazion - symptoms, meaning, therapy.
Acta Psychiatr Scand 66: 451-458
Nuller Y L, Mickalenko I N (1988) Affective psychoses. Meditsina,
Leningrad
Shader R I (1994) Manuel of psychiatric therapeutics, 2nd edn.
Little, Brown and Company, Boston
Volavka J, Anderson B, Koz G (1982) Naloxone and naltrexone in
mental illness and tardive dyskinesia. Ann NY Acad Sci 97-102


----------



## Visual (Oct 13, 2010)

Huggy Bear said:


> My two cents: I think this Naloxone study is a hoax. If it was so succesful, why did others not repeat it and why do we not hear more success stories following Naloxone administration?
> 
> I had Naloxone admininstered twice. First time 4mg, second time 12mg (i.e. higher than any dose in the study). The effect was zero.
> 
> But I have written this before...


Sorry that you have had this 20+ years









I agree that there is no one cure, though I have had improvement with dopamine agonists and anti-seizure meds and thus freely speak of it.

Was wondering what other meds you have tried over the years?


----------



## 35467 (Dec 31, 2010)

"My two cents: I think this Naloxone study is a hoax. If it was so succesful, why did others not repeat it and why do we not hear more success stories following Naloxone administration? I had Naloxone admininstered twice. First time 4mg, second time 12mg (i.e. higher than any dose in the study). The effect was zero. But I have written this before"

I don´t think the trail is a hoax. First of all most patients had not had DP for many years and therefor more responsive. Secondly, the half-life of naloxone is 60.min and many recieved multiple doses of total 50.mg. One didn´t respond at all. The shot half-life is a problem so multiple doses is essensial.

I have besides that read 2.interesting studies were normal were given kappa agonist witch gave symptoms within the Oxford depersonalization scale in one of the studies the effect was blocked by naloxone. Nalmefene can block the effects a 2. kappa agonist in doses around 20.mg. The drug has a half life around 15-hours in the oral form. Nalmefene will be out in the coming year.


----------



## 35467 (Dec 31, 2010)

@Huggy bear

Naloxone can never be a treatment because of the short half -life. They could replicate the russian study -there you are right. Regaring nalmefene -the drug itn´t out yet but it will get approvel for alcohol craving. I think it is easy to get a trail with a drug if it is approved for one indication -than if it isn´t approved for anything.It has probleby been the problem with a DP trail.

http://www.the-alcoholism-guide.org/new-drug-for-alcoholism.html


----------

