Atypical Antipsychotics

Has anyone had experience with Serdolect (sertindole)? I'll start using it tomorrow for possible simple schizophrenia or schizoid disorder (to resolve blunted affect and apathy). I'm unsure whether or not it will work, and I've already wasted months of time with the dozens of medicines I've tried. I've already tried a typical antipsychotic, penfluridol (Semap), and it did more bad than good: it worsened my feelings of emptiness, which I attribute to its antidopaminergic effect.

I'm aware that atypical antipsychotics antagonize the 5-HT2A, D4 and D2 receptors. Seeing how I feel much better in conditions involving decreased serotonin (eg murky weather), I've little doubt that decreasing serotonergic activity could be beneficial, but dopamine agonists (such as bupropion) have also helped, so I can't help but doubt that D2 and D4 antagonists could.
In fact, bupropion (Welbutrin) was the first antidepressant that actually worked: using it, I felt more motivated, and even felt emotion aside from emptiness. However, I'm not sure if this was because it alleviated blunted affect, emptiness, or anhedonia (probably the latter), and I might still have felt less emotion than normal.

Could anyone share his experiences with sertindole or atypical antipsychotics in general? How long does it take for sertindole to work? What are its (side-)effects on mood? Suppose that I'm wrong and I'm suffering from emptiness instead of actual loss of affect, could sertindole still work?

Please help me if you can. I've been switching from the one drug to the other for months now, and these dilemma's are driving me insane - even more insane, I mean. Many thanks in advance to anyone who could give me advise.

It sounds like your symptoms are similar to mine (apathy,
anhedonia, emotional blunting and so on). I've been trying
different drugs for about 7 years. Of the atypical antipsychotics
I tried, risperidone made me worse, even at low doses, while
sulpiride at low doses resolved my apathy, but only for a week or
two, as I developed tolerance to its activating effects. Pramipexole,
a dopamine D3/D2 agonist was effective against anhedonia, but
only for a week or two. Selegiline, a MAO-B inhibitor, resulted in
improvement for a couple of days, after which its benefits were lost.
Methylphenidate (Concerta) is somewhat effective against apathy
and improves wakefulness, but I keep developing tolerance to it,
and have to increase the dose.

Right now, my planned next step is to attempt boosting the
methylphenidate with L-dopa. I also look forward to testing
modafinil, guanfacine, memantine and dextroamphetamine.

Thanks for you suggestions. I guess antipsychotics don't really work for me. My psychiatrist said the Sertindole would start working in the weekend, and so far, I've only experienced a slight worsening of symptoms, along with a cold.

I've used methylphenidate for several years, and I'm still not sure if the onset of my dysthymia four years back was partly because or despite of it. At that time, it slowed my growth and made me anxious (even obsessive-compulsive), although I doubt that those should be issues if you're adult and feel apathetic. Because of the tolerance, however, I think there are better options.

Modafinil, in addition to dopamine, also enhances NA activity, and in my experience, noradrenergic medicines like Reboxetine blunt my creativity. It also inhibits GABA activity, and I feel better with GABA agonists like Temesta. Guanfacine increases adrenergic activity, which wouldn't really resolve blunted affect. I wouldn't know about memantine. Dextroamphetamine also increases serotonin, and that's probably the last neurotransmitter I need.

Pramipexole, however, seems interesting, probably more than the Welbutrin I used until a month ago. I'll ask my shrink about it.

I'm no doctor, but I think Tianeptine would be ideal for me. Symptoms improve in darkness (eg winter and fall, evening, cloudy weather). Melatonin hasn't helped, and seeing how serotonin is a mood blunter and an excess may be responsible for the negative sympatomatology of schizophrenia, I guess a selective serotonin reuptake enhancer could work for me. Unfortunately, my psychiatrist doesn't want to prescribe it.

Oblomov wrote:Thanks for you suggestions. I guess antipsychotics don't really work for me.

That's what I thought after trying risperidone. However, I've since
realised that forming premature and far-reaching conclusions is not
a good idea. Different compounds have different binding profiles,
and low and high doses of a single agent can have radically
different effects. For example, most of the so-called dopamine D2
receptor antagonists also block D1 and various adrenergic receptors
and some are anticholinergic. An example of the effect of dose is
the benzamide class of anti-psychotics (sulpiride and amisulpride)
that boost dopaminergic activity at low doses (e.g. 50 mg/day for
amisulpride) due to preferential antagonism of pre-synaptic
receptors (autoreceptors) and have been proven effective against
dysthymia.

I've used methylphenidate for several years, and I'm still not sure if the onset of my dysthymia four years back was partly because or despite of it. At that time, it slowed my growth and made me anxious (even obsessive-compulsive), although I doubt that those should be issues if you're adult and feel apathetic. Because of the tolerance, however, I think there are better options.

Possibly, although there may be solutions to the problem of
tolerance. One of those might be the benzamide antipsychotics
mentioned above - although that proved insufficient for me, you
may have better luck. As I mentioned, I plan to try augmentation
with L-dopa too. Selegiline is another possibility. Furthermore,
if I have to resort to dextroamphetamine, I'll test if methylphenidate
can reduce the effective dose of amphetamine. Minimising the use
of amphetamines is advisable due to the potential of neurotoxicity.

Modafinil, in addition to dopamine, also enhances NA activity, and in my experience, noradrenergic medicines like Reboxetine blunt my creativity.

Modafinil is less noradrenergic than the other stimulants mentioned,
as demonstrated by its lesser cardiovascular effects.

It also inhibits GABA activity, and I feel better with GABA agonists like Temesta.

Benzodiazepines (Temesta and others) reduce anxiety and some
like to [ab]use them for euphoric (recreational) purposes. However,
they also reduce mental acuity and alertness, so if you're struggling
with apathy, emotional blunting, attention deficits, etc. you should
probably avoid them.

Guanfacine increases adrenergic activity, which wouldn't really resolve blunted affect.

Actually, it reduces adrenergic activity - that's why it's used as an
antihypertensive agent. Another reason why it's interesting is that
it appears to have beneficial effects on the prefrontal cortext, which
plays a major role in executive functions and working memory.

I wouldn't know about memantine.

It's a NMDA-antagonist derived from amantadine. Some studies
have found that it has antidepressive effects, although it's mostly
used for Alzheimer's.

Dextroamphetamine also increases serotonin, and that's probably the last neurotransmitter I need.

Its serotonergic effects are rather modest at low doses.

I'm no doctor, but I think Tianeptine would be ideal for me. Symptoms improve in darkness (eg winter and fall, evening, cloudy weather). Melatonin hasn't helped, and seeing how serotonin is a mood blunter and an excess may be responsible for the negative sympatomatology of schizophrenia, I guess a selective serotonin reuptake enhancer could work for me. Unfortunately, my psychiatrist doesn't want to prescribe it.

Has he stated any particular reasons for that? Tianeptine is not
particularly controversial (unlike Ritalin and the like).

Possibly, although there may be solutions to the problem of
tolerance. One of those might be the benzamide antipsychotics
mentioned above - although that proved insufficient for me, you
may have better luck. As I mentioned, I plan to try augmentation
with L-dopa too. Selegiline is another possibility.

I've considered L-dopa and Selegiline, too, but my suggestions were dismissed. I was given Welbutrin instead, which has a pesky 1/3 noradrenergic effect. It eventually worked, but because of my earlier experiences with Edronax (which made me feel even more depersonalized), I switched to L-tyrosine, believing, erroneously, that it was less noradrenergic than Welbutrin.

Benzodiazepines (Temesta and others) reduce anxiety and some
like to [ab]use them for euphoric (recreational) purposes. However,
they also reduce mental acuity and alertness, so if you're struggling
with apathy, emotional blunting, attention deficits, etc. you should
probably avoid them.

I use lorazepam only now and then when feeling particularly frustrated: I avoid using them often because they're addictive. When I use it, I think I actually function better because it allays my anxiety.

Has he stated any particular reasons for that? Tianeptine is not
particularly controversial (unlike Ritalin and the like).

At first, he said it was just another copy of other antidepressants like fluoxetine. When I told him it was the only drug (as far as I know) which has the opposite effect (enhancing rather than inhibiting serotonin reuptake), he resorted to saying that too little was known about it, and he "didn't want to use me as a research animal."

Oblomov wrote:I've considered L-dopa and Selegiline, too, but my suggestions were dismissed. I was given Welbutrin instead, which has a pesky 1/3 noradrenergic effect. It eventually worked, but because of my earlier experiences with Edronax (which made me feel even more depersonalized), I switched to L-tyrosine, believing, erroneously, that it was less noradrenergic than Welbutrin.

Tyrosine and (L- and D,L-)phenylalanine had no noticeable effects
on me, even in combination with selegiline. Selegiline itself is also
not free from noradrenergic effects (through several mechanisms).

Someone on the schizoid personality forum experienced seriously
worsened depersonalisation with Edronax a few weeks/months
ago, and my experience with it is somewhat similar: it made me,
if not more depersonalised, at least more emotionally blunted and
schizoid. Before Edronax, I was emotionally hypersensitive
especially to negative experiences - probably due to depression.
Soon after starting it, I became emotionally flattened and highly
resistant to experiences that used to upset me, and these effects
have lasted to this day, even though it's been years since I stopped
taking the Edronax.

I've visited another psychiatrist today. I'm rather doubtful about his competence, though, as he has the same arrogance all my previous psychiatrist have had. When I said I feel bad in arid weather because of the positive ions, which increase serotonin production (1) (2) (3), he saw this a delusion (calling it "borderline magical thinking"), and a frank symptom of psychosis. What the hell is wrong with these people?

Anyway, he prescribed Abilify, but because I've already had a very bad experience with antipsychotics, and I've come to fear that, like Reboxetine, they may have lasting side effects, I'm rather doubtful about drugs which have antagonism, even partial, of my dopaminergic system. I don't find much information about the effects of Apiprazole on latent inhibition, creativity or imagination, but someone on these forums said that it might have reduced his/her imagination. Being a schizoid and a writer, fantasy is paramount to me, and I will have nothing interfere with that ability.

I hate these dilemma's… can someone help?

Oblomov wrote:I've visited another psychiatrist today. I'm rather doubtful about his competence, though, as he has the same arrogance all my previous psychiatrist have had. When I said I feel bad in arid weather because of the positive ions, which increase serotonin production (1)[(2)][url=http://www.static-sol.com/library/articles/air%20ion%20effects.htm](3)), he saw this a delusion (calling it "borderline magical thinking"), and a frank symptom of psychosis. What the hell is wrong with these people?

Whilst regarding it a "frank symptom of psychosis" is an
exaggeration, I can understand the comment of "borderline
magical thinking", because that's what it sounds like, unless
one has taken part of the same information as you have and
made the same interpretations thereof. Looking at your
statement as worded above, you seem to present your
hypothesis (linking weather, ions, serotonin and mood) as if
it were a proven certainty. I find that quite hasty, but more
importantly, it's not the kind of information to present to a
psychiatrist you've just met.

Anyway, he prescribed Abilify, but because I've already had a very bad experience with antipsychotics, and I've come to fear that, like Reboxetine, they may have lasting side effects, I'm rather doubtful about drugs which have antagonism, even partial, of my dopaminergic system. I don't find much information about the effects of Apiprazole on latent inhibition, creativity or imagination, but someone on these forums said that it might have reduced his/her imagination. Being a schizoid and a writer, fantasy is paramount to me, and I will have nothing interfere with that ability.

I hate these dilemma's… can someone help?

Aripiprazole (APZ) stimulates dopamine autoreceptors, so I would
expect it do reduce DA synthesis and release, which would normally
result in many adverse effects, but APZ has a variety of other full/
partial agonist and antagonist activities, so the end result is difficult
to predict from a theoretical point of view.

In my case, I think the lack of fantasy/creativity is primarily a result
of generalised apathy and anhedonia.

You're different from most schizoids. They don't tend to complain
about lack of imagination, creativity, negative feelings. Indeed,
many are grateful for the stability provided by emotional blunting.

sum1 wrote:Looking at your statement as worded above, you seem to present your hypothesis (linking weather, ions, serotonin and mood) as if it were a proven certainty.

Oh, I don't think it's a certainty. That comment was an expression of my frustration at how psychiatrists treat their patients - almost like computers. I've already had bad experiences with psychiatrists earlier, and the more I speak psychiatrists, the more I become antipsychiatrist.

I realize that my frustration was an unusual occurrence. I think I've been undergoing some emotional change over the past few days, probably because of the phenylalanine… I've read that schizoids have an excess of tryptophan metabolites and a lack of tyrosine metabolites, and PhA restores both those imbalances… My symptoms start to liken those of depression more every day, so I'm returning to my former state. The PhA makes me sleepy, but I've started using the Welbutrin again today, and that'll probably counter the somnolence.

I think full dopamine agonism would be better than partial in my case. Symptoms like thought disorder and distraction don't seem too problematic for me. I'm aware the D2 receptors may be involved in distress, I have no trouble at all with feeling increased distress - I guess I'd be grateful for it.

sum1 wrote:You're different from most schizoids. They don't tend to complain about lack of imagination, creativity, negative feelings. Indeed, many are grateful for the stability provided by emotional blunting.

Perhaps it isn't schizoid personality disorder. It could be schizotypy, or schizophrenia, or depression. I'm only 17, so it could still be prodromal.

Edit: I've just read that bupropion increases dopamine transporter mRNA in the ventral tegmentum and substantia nigra. Could this cause the medicine to backfire in the long run? If I build up tolerance to it, it'll end up doing more harm than good.

Oblomov wrote:I think full dopamine agonism would be better than partial in my case. Symptoms like thought disorder and distraction don't seem too problematic for me. I'm aware the D2 receptors may be involved in distress, I have no trouble at all with feeling increased distress - I guess I'd be grateful for it.

There are no direct dopamine agonists acting at all receptors, so
you would have to use indirect ones (stimulants, precursors...).
The direct agonists with a high preference for D2 as opposed to D1,
are less than ideal because they stimulate autoreceptors, thus
reducing endogenous DA activity, at the same time as they cannot
fully substitute for it.

I tried pramipexole, a D3/D2 full agonist, and in the beginning there
were periods, up to 12 hours or so, when it seemed to be working
great. Divided attention, sensory experience (vision/hearing),
reaction time and pleasure were improved to a level I hadn't
experienced for many years. These effects were seen in the first
week or so, during which I also had a few hypotensive attacks
(almost passed out) and suddent onsets of sleepiness. The
sleepiness is all that remains of its effects now, so I no longer
take it. I'm fairly certain that the adverse effects are/were due to
autoreceptor stimulation.

For comparison, sulpiride, which preferentially blocks autoreceptors,
worked consistently for two weeks with minimal adverse effects.
However, the positive effects were qualitatively different - initially,
the activating effects were almost too intense (near agitation, but
without adrenergic/cardiovascular activation). Working memory,
motivation, attention and executive function improved to a greater
extent than with pramipexole, but there was very little effect on
pleasure, divided attention, sensory processing and reaction time.

Since I tried pramipexole before sulpiride, it's possible that the
former modified the effects of the latter, by adaptive changes in
neurophysiology.

Edit: I've just read that bupropion increases dopamine transporter mRNA in the ventral tegmentum and substantia nigra. Could this cause the medicine to backfire in the long run? If I build up tolerance to it, it'll end up doing more harm than good.

I imagine that bupropion tolerance would be somewhat similar to
cocaine or methylphenidate tolerance. In my case, MPH tolerance
developed fairly rapidly, but upon cessation, no withdrawal effects
were noticeable - which is a good sign - and I found that selegiline
is more unpleasant to quit than MPH.