![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 22 of 22. This is the beginning of the thread.
Posted by mogger on September 28, 2014, at 23:38:35
Hi there,
I have added Risperdal to my cocktail and it has made a substantial difference to both my depression and killed my anxiety/ocd. I am encouraged by marked improvement however my libido has plummeted. I am at .75mg a day of Risperdal which I think is a low dose and I don't think I could go any lower without the depression/anxiety returning so I am in a major predicament. I have tried meds for 21 years and this seems to be the best med other than lamictal I have tried so I don't want to go off it. Has anyone ever heard that Invega has lessened side effects i.e. perhaps less sexual dysfunction or am I screwed? I don't want to come off Risperdal so the only thing I can think of is to try decreasing my 150mgs of sertraline? Many thanks for your thoughts and experiences,
Joseph
Posted by ed_uk2010 on October 1, 2014, at 15:22:41
In reply to Risperdal helping but loss of libido, posted by mogger on September 28, 2014, at 23:38:35
> Hi there,
>
> I have added Risperdal to my cocktail and it has made a substantial difference to both my depression and killed my anxiety/ocd. I am encouraged by marked improvement however my libido has plummeted. I am at .75mg a day of Risperdal which I think is a low dose and I don't think I could go any lower without the depression/anxiety returning so I am in a major predicament. I have tried meds for 21 years and this seems to be the best med other than lamictal I have tried so I don't want to go off it. Has anyone ever heard that Invega has lessened side effects i.e. perhaps less sexual dysfunction or am I screwed? I don't want to come off Risperdal so the only thing I can think of is to try decreasing my 150mgs of sertraline? Many thanks for your thoughts and experiences,
>
> JosephHi Joseph,
Very pleased to hear that Risperdal is helping your symptoms.... and no, you are not screwed.
The mechanism by which risperidone causes sexual dysfunction is quite well understood. Even at low doses, it can produce quite a marked elevation of prolactin levels. Prolactin is a hormone which is vital in women during breastfeeding because it allows milk to be produced. In men, its function is less clear but it is always present in the blood at a low level. Given your sexual problems, you should ask your doctor to do a blood test for prolactin.
Certain antipsychotics, notably risperidone, paliperidone (Invega) and amisulpride (Solian) can produce large increases in the blood levels of prolactin. In women, the increase is often even worse. Invega causes just as much sexual dysfunction as Risperdal so is not an option.
Anyway, the increase in prolactin produces a decrease in libido and sexual dysfunction. Part of the reason for this may be that high prolactin causes a drop in testosterone levels.
So.... how to deal with it. There are several options.
Some antipsychotics produce very little change in prolactin levels eg. quetiapine (Seroquel). Olanzapine (Zyprexa) often causes a marginal increase, much less than Risperdal. Aripiprazole (Abilify) is totally unique because it actually reduces prolactin levels. If you respond well to any of the above you could switch. If not, there is the option of adding a tiny dose of Abilify. When added to Risperdal, Abilify can reverse the increased prolactin and restore sexual function. Because aripiprazole acts as a partial agonist (stimulant) of the dopamine receptors in the pituitary gland, it prevents prolactin from being released. This can improve sexual function. Assuming your prolactin levels come back as high and you don't respond as well to other antipsychotics as Risperdal, I suggest adding 2mg of Abilify and then increasing to 5mg after a week or two. Your prolactin levels should then drop over the next few weeks, testosterone levels should increase and you should notice an improvement in both libido and sexual function.
Hope this helps. Do let me know if you have any further questions.
Posted by SLS on October 1, 2014, at 16:10:34
In reply to Advice » mogger, posted by ed_uk2010 on October 1, 2014, at 15:22:41
Hi Ed.
I would have said exactly the same thing - if I only were to know as much as you do! (Never happen).
:-)
Great post. 100% accurate.
I didn't know about the use of Abilify. Great tip.
- Scott
> > Hi there,
> >
> > I have added Risperdal to my cocktail and it has made a substantial difference to both my depression and killed my anxiety/ocd. I am encouraged by marked improvement however my libido has plummeted. I am at .75mg a day of Risperdal which I think is a low dose and I don't think I could go any lower without the depression/anxiety returning so I am in a major predicament. I have tried meds for 21 years and this seems to be the best med other than lamictal I have tried so I don't want to go off it. Has anyone ever heard that Invega has lessened side effects i.e. perhaps less sexual dysfunction or am I screwed? I don't want to come off Risperdal so the only thing I can think of is to try decreasing my 150mgs of sertraline? Many thanks for your thoughts and experiences,
> >
> > Joseph
>
> Hi Joseph,
>
> Very pleased to hear that Risperdal is helping your symptoms.... and no, you are not screwed.
>
> The mechanism by which risperidone causes sexual dysfunction is quite well understood. Even at low doses, it can produce quite a marked elevation of prolactin levels. Prolactin is a hormone which is vital in women during breastfeeding because it allows milk to be produced. In men, its function is less clear but it is always present in the blood at a low level. Given your sexual problems, you should ask your doctor to do a blood test for prolactin.
>
> Certain antipsychotics, notably risperidone, paliperidone (Invega) and amisulpride (Solian) can produce large increases in the blood levels of prolactin. In women, the increase is often even worse. Invega causes just as much sexual dysfunction as Risperdal so is not an option.
>
> Anyway, the increase in prolactin produces a decrease in libido and sexual dysfunction. Part of the reason for this may be that high prolactin causes a drop in testosterone levels.
>
> So.... how to deal with it. There are several options.
>
> Some antipsychotics produce very little change in prolactin levels eg. quetiapine (Seroquel). Olanzapine (Zyprexa) often causes a marginal increase, much less than Risperdal. Aripiprazole (Abilify) is totally unique because it actually reduces prolactin levels. If you respond well to any of the above you could switch. If not, there is the option of adding a tiny dose of Abilify. When added to Risperdal, Abilify can reverse the increased prolactin and restore sexual function. Because aripiprazole acts as a partial agonist (stimulant) of the dopamine receptors in the pituitary gland, it prevents prolactin from being released. This can improve sexual function. Assuming your prolactin levels come back as high and you don't respond as well to other antipsychotics as Risperdal, I suggest adding 2mg of Abilify and then increasing to 5mg after a week or two. Your prolactin levels should then drop over the next few weeks, testosterone levels should increase and you should notice an improvement in both libido and sexual function.
>
> Hope this helps. Do let me know if you have any further questions.
>
>
>
>
Posted by ed_uk2010 on October 1, 2014, at 16:44:53
In reply to Re: Advice » ed_uk2010, posted by SLS on October 1, 2014, at 16:10:34
>I didn't know about the use of Abilify. Great tip.
Yeah it works pretty well for high prolactin caused by risperidone and paliperidone. Doesn't seem to work as well with amisulpride but may still produce some reduction in prolactin.
Average dose for hyperprolactinaemia is 5mg Abilify. Varies from 2-10mg though.
And anyway, stop being so complimentary!! It is nice though :)
Take care,
Ed
Posted by mogger on October 2, 2014, at 10:59:21
In reply to Re: Advice » SLS, posted by ed_uk2010 on October 1, 2014, at 16:44:53
Thanks so much for your advice! I am hoping my doctor is open to adding Abilify as he has said it can exacerbate ocd and has a high incidence for akathisia which I tend to get. I see Bromocriptine is also used to treat Risperidone hyperprolactinaemia as it is a dopamine agonist. Many thanks for your help!
Joseph
Posted by ed_uk2010 on October 3, 2014, at 7:18:05
In reply to Re: Advice, posted by mogger on October 2, 2014, at 10:59:21
>Thanks so much for your advice! I am hoping my doctor is open to adding Abilify as he has said it can exacerbate ocd and has a high incidence for akathisia which I tend to get. I see Bromocriptine is also used to treat Risperidone hyperprolactinaemia as it is a dopamine agonist. Many thanks for your help!
>
> JosephHi,
There are several concerns about bromocriptine:
1. As a full dopamine D2 agonist, it can potentially cause or aggravate psychiatric symptoms.
2. There is a risk of certain irreversible side effects after long-term use eg. fibrosis/scarring of the heart valves or lung tissue. The frequency of minor side effects is also rather high!
As such, it is no longer a popular treatment for hyperprolactinemia of any cause. Cabergoline and quinagolide are preferred for hyperprolactinemia causes by pituitary tumors. Aripiprazole is preferred for hyperprolactinemia causes by antipsychotics.
First, you should have a blood test to check your prolactin level. Assuming it's elevated, you could add 2mg or 2.5mg of aripiprazole per day. A low starting dose should help to minimise adverse effects such as akathisia, or any other symptom exacerbation. If akathisia occurs with Abilify, it tends to wear off as you adjust to the medication.... unlike older antipsychotics. You could potentially use a benzodiazepine for a few days if it makes you restless. If tolerated, you could then increase Abilify to 5mg and repeat the prolactin level after a few weeks. Sexual function should improve within a few weeks.
Some evidence which you may find helpful....
Here is a little study in women, who tend to suffer greater elevations in prolactin (hyperprolactinemia) and more symptoms. It suggests that aripiprazole exerts an effect even at 3mg per day, and that doses above 6mg are not normally needed. In practice, 2-5mg would be used, unless you want to measure awkward doses using Abilify liquid!
J Clin Psychopharmacol. 2010 Oct.
Dose-dependent effects of adjunctive treatment with aripiprazole on hyperprolactinemia induced by risperidone in female patients with schizophrenia.
Abstract
Hyperprolactinemia is a frequent consequence of treatment with risperidone. Recent studies have suggested that aripiprazole, a partial dopamine agonist, reduces the prolactin response to antipsychotics. Thus, we examined the dose effects of adjunctive treatment with aripiprazole on the plasma concentration of prolactin in patients who had elevated prolactin levels because of risperidone treatment.
Aripiprazole was concomitantly administrated to 16 female patients with schizophrenia receiving 2 to 15 mg/d of risperidone. Dosages of aripiprazole were gradually increased from 3 to 12 mg/d with 2- to 4-week intervals. Sample collections for prolactin were conducted before aripiprazole administration (baseline) and 2 to 4 weeks after the dose escalation of aripiprazole and just before next dose escalation. The samples were taken just before the morning dose.
The plasma concentration of prolactin during aripiprazole administration (3, 6, 9, or 12 mg/d) was significantly lower than that at baseline. The mean (±SD) percent reductions at 3, 6, 9, and 12 mg/d were 35% ± 14%, 54% ± 17%, 57% ± 19%, and 63% ± 17%, respectively. However, neither the plasma concentration of prolactin nor the reduction ratio differed among the dosages of 6, 9, and 12 mg/d of aripiprazole. Three out of 8 patients with amenorrhea improved after 12 mg/d of aripiprazole.
The present study suggests that adjunctive treatment with aripiprazole reduces the prolactin concentration that had been increased because of risperidone treatment. The effect occurs even when a low dosage (3 mg/d) of aripiprazole was used and achieves a plateau at dosages beyond 6 mg/d.
..........................................................
Here is another study looking at the efficacy of adding aripiprazole. It shows that aripiprazole normalised prolactin levels in the majority of patients treated with risperidone, but was only of marginal use when added to amisulpride or sulpiride. (Hyperprolactinemia caused by the latter two drugs is difficult to manage).
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1.
Differential add-on effects of aripiprazole in resolving hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics.
Abstract
Hyperprolactinemia is associated with typical antipsychotic agents and atypical antipsychotics such as risperidone and amisulpride. This study investigates the effects of 8-week adjunctive treatment with aripiprazole in patients with hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics (amisulpride and sulpiride). Aripiprazole was administered to 24 patients with antipsychotic-induced hyperprolactinemia. The doses of pre-existing antipsychotics were fixed, while the aripiprazole dose was 5-20 mg/day during the 8-week study period. Serum prolactin levels were measured at weeks 4 and 8. Symptoms and side effects were assessed using the Positive and Negative Syndrome Scale (PANSS), Arizona Sexual Experience Scale, Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Barnes Akathisia Scale, and metabolic measures at weeks 2, 4 and 8.
Mean (standard error) prolactin levels decreased from 77.0±13.3 ng/mL to 18.3±2.1 ng/mL (p<0.001 vs. baseline), from 144.9±24.4 ng/mL to 127.5±21.7 ng/mL (p=0.099 vs. baseline) and 71.4±24.6 ng/mL to 43.3±14.7 ng/mL (p=0.106 vs. baseline) for those taking risperidone, amisulpride, and sulpiride, respectively.
For those who took risperidone before the study started, 14 of 15 (93.3%) patients had normalized prolactin levels, while only 1 of 10 (10%) taking benzamide antipsychotics had normalized prolactin levels. The PANSS score improved significantly, and aripiprazole had no significant influence on metabolic measures or scales of movement side effects.
Adjunctive aripiprazole treatment reversed effectively hyperprolactinemia induced by risperidone, but was less effective for that induced by benzamide antipsychotics.
...There are various other little studies too, it's certainly the best established option so far.
Posted by mogger on October 6, 2014, at 10:22:59
In reply to Aripiprazole (Abilify) » mogger, posted by ed_uk2010 on October 3, 2014, at 7:18:05
Thank you Ed. Surprisingly my prolactin levels came back normal so I am not sure what has caused the plummet in libido! I am now trying a slight decrease in risperdal to see if that helps. Many thanks again for your help,
Joseph
Posted by ed_uk2010 on October 7, 2014, at 17:50:25
In reply to Re: Aripiprazole (Abilify) » ed_uk2010, posted by mogger on October 6, 2014, at 10:22:59
Trigger - for anyone not wanting to hear about male sexual function.
Hi Joseph,
So, apart from risperidone and sertraline, what other meds (and doses) are on you at the moment?
Is the addition of risperidone that only change you've made in recent times or have other meds be started/stopped/adjusted as well? How long have you actually been taking risperidone for? It appears to have made quite a difference :)
Also, do you have a specific psych diagnosis, if you don't mind me asking, and any major physical health problems?
Sorry for all the questions. But lack of information and knowledge leads to bad, worthlesss advice! Sometimes frankly dangerous advice. You see it so much online. Poster A tells poster B what/or not to take without establishing any details of their age, med history, diagnosis, general health, med regimen etc etc.
If you don't mind me asking, has ED become a issue? If so, there are plenty of things which can be done about that. Few such treatments affect libido directly but most are likely to produce some indirect increase in desire. Greater blood flow and erections can improve confidence, sensation.....desire....and hence libido.
Posted by mogger on October 10, 2014, at 10:37:00
In reply to Sure this problem can be resolved.Possible TRIGGER » mogger, posted by ed_uk2010 on October 7, 2014, at 17:50:25
Hi Ed,
I am on
300mg Lamotrigine
90mg Buspar
60mg Remeron
.5mg Clonazepam (tapering off it)I am an athlete so I am fit as a fiddle. Never had a problem before. I think tapering off clonazepam has had something to do with lack of libido as withdrawals have made me disconnected and feeling awful in general. I have OCD and clinical depression of 26 years. Being down from .75mg to .5mg of Risperdal for a week has helped for sure with libido. Unfortunately since coming down on Risperdal some depression has come back which was helping at .75mgs. I am thinking of trying switching to Invega to see if there is any difference. I have read but I can't find the study that there is another theory behind lack of libido and Risperdal.
Posted by ed_uk2010 on October 11, 2014, at 23:51:29
In reply to Re: Sure this problem can be resolved.Possible TRIGGER » ed_uk2010, posted by mogger on October 10, 2014, at 10:37:00
Hi Joseph,
I've been working on a proper reply but it's not ready yet. Quick questions.
> I am on
>
> 300mg Lamotrigine
> 90mg Buspar
> 60mg Remeron
> .5mg Clonazepam (tapering off it)I thought you were on sertraline too? Was that stopped?
Could you tell me, apart from Risperdal, which other antipsychotics have you tried? Any effects good or bad? If you can remember the doses and how long you took them that would be great.
Are you still on 0.5mg Risperdal? How are you doing? When do you take it? - Any fluctuation in symptoms across the day?
Hope you are well.
Posted by mogger on October 12, 2014, at 0:01:23
In reply to Re: Sure this problem can be resolved. » mogger, posted by ed_uk2010 on October 11, 2014, at 23:51:29
Ed sorry yes I am still on 150mgs of sertraline a day. Today was pretty rough with quite a bit of depression coming back. I have been at .5mgs from .75mgs for 10 days now. I have tried zyprexa, seroquel, latuda and saphris. I have been a non responder and initially risperdal put me almost in remission for about 3 months until the lack of libido popped up. I shall talk to my doctor on monday and get his thoughts.
Posted by SLS on October 12, 2014, at 9:10:14
In reply to Re: Sure this problem can be resolved. » ed_uk2010, posted by mogger on October 12, 2014, at 0:01:23
> Ed sorry yes I am still on 150mgs of sertraline a day. Today was pretty rough with quite a bit of depression coming back. I have been at .5mgs from .75mgs for 10 days now. I have tried zyprexa, seroquel, latuda and saphris. I have been a non responder and initially risperdal put me almost in remission for about 3 months until the lack of libido popped up. I shall talk to my doctor on monday and get his thoughts.
Risperidone (Risperdal) is the most potent 5-HT2a antagonist available. It is also selective for this receptor relative to other 5-HT receptors. Perhaps this is important in your response to risperidone. If so, you might be able to use the following antidepressant drugs as replacements:
nortriptyline (Pamelor)
amitriptyline (Elavil)
clomipramine (Anafranil)
mirtazepine (Remeron)
nefazodone (Serzone)
mianserin (Lumin, Tolvon)If such a substitution is effective, you would avoid the hyperprolactinemia produced by risperidone.
- Scott
Posted by ed_uk2010 on October 12, 2014, at 12:51:21
In reply to Re: Sure this problem can be resolved. » mogger, posted by SLS on October 12, 2014, at 9:10:14
>mirtazepine (Remeron)
Hi Scott,
The thing is. Mogger is already on mirtazapine at a high dose, and his prolactin came back normal.
Posted by ed_uk2010 on October 12, 2014, at 20:51:46
In reply to Re: Sure this problem can be resolved. » ed_uk2010, posted by mogger on October 12, 2014, at 0:01:23
Hi Joseph,
>Today was pretty rough with quite a bit of depression coming back. I have been at .5mgs from .75mgs for 10 days now. I have tried zyprexa, seroquel, latuda and saphris. I have been a non responder and initially risperdal put me almost in remission for about 3 months until the lack of libido popped up. I shall talk to my doctor on monday and get his thoughts.
Well, Risperdal is a very potent drug in terms of what can be achieved with low doses. Clearly, small changes in dose can make a lot of difference. I'd like to give you are few idea to discuss with your pdoc.
Even in psychotic illness, there's been a change in dosing over time. Risperdal was initially launched with a 4-8mg/day target dose for schizophrenia. This was not a good idea. It's now recognised that first episode psychosis often responds well to about 2mg per day and even in chronic unremitting psychosis, increasing above 4mg doesn't usually offer much additional benefit. It's now known from brain scans (PET) that even 2mg per day of Risperdal can block around 65% of D2 dopamine receptors in the brain. This is about the minimum needed to treat psychotic illness or acute manic episodes. Of course, you are not psychotic, nor are you manic, so the optimal dose for you will be different, and based on your response so far, considerably less.
You could of course try paliperidone PR (Invega) next. Overall, the effects are usually very similar to risperidone because most of the risperidone you take is metabolised to paliperidone anyway. In terms of side effects, risperidone causes a slightly higher incidence of post-dose drowsiness and hypotension/dizziness. Paliperidone's much slower absorption makes dizziness uncommon. At equivalent doses, paliperidone is slightly more likely to elevate prolactin but YMMV! Insomnia is also more frequent with paliperidone, probably because night time doses of risperidone can help sleep. Risperidone has a mild antihistamine sedative effect which paliperidone almost completely lacks. Apart from that, the pharmacological properties are similar.
The main issues I think you should consider before looking to switch meds are:
1. For someone sensitive to small doses, paliperidone offers much less flexibility than risperidone. The lowest tablet strength of Invega is 1.5mg, which cannot be halved, and there is no liquid formulation. Invega 1.5mg generally has an effect similar to your current 0.5mg to 0.75mg dose. Unlike risperidone, which is very well absorbed, oral paliperidone is poorly absorbed - this accounts for the higher doses needed. The amount of paliperidone you absorb also depends a great deal on what you eat with it, consistency is therefore important. Risperidone is well absorbed regardless. Invega 1.5mg plus a burger might = risperidone 0.75mg. Invega 1.5 plus a glass of water might = risperdone 0.5mg!! This isn't precise but you get the idea. In studies, bioavailability could be increased by as much as 60% just by taking Invega alongside a normal sized meal with some fat content.
2. What are the cost implications of Invega? No doubt it's expensive. Would your insurance cover it? It would be great if your doc had some samples of 1.5mg to try, but I think he's more likely to have samples of say 6mg, which probably aren't suitable. No doubt Janssen have produced a lot of 6mg samples, they recommend it as the starting dose for almost all adults. The 1.5mg tablet is supposed to be for those with kidney impairment.
If you try Invega 1.5mg, it might suit, it might not :) There is no lower strength if 1.5mg is too strong, and I doubt the higher strengths would be suitable considering your sensitivity to risperidone. If I were you, I might just base my decision on the presence or absence of 1.5mg samples.
Sadly, it's already clear that 0.5mg Risperdal is not enough. 0.75mg was a bit too much - great efficacy, some side effects. You could try anything in between using the risperidone liquid. Many people will say 'don't bother, these doses are placebos'. That's BS. Lower doses potently block 5-HT2a receptors.... but you already get that from mirtazapine 60mg so it doesn't really explain risperidone's benefits or side effects for you. Risperidone also blocks 5-HT7 receptors, which *may* be antidepressant. Latuda didn't help you though and it's very potent at this receptor. Hmm. I think you're actually benefiting from the mild D2 antagonism created by the low dose of risperidone. Too little D2 blockage won't help, too much D2 blockage can reduce libido - you need to get the dose right. Ultra-low doses of antipsychotics are hardly a new strategy for anxiety and depression. Flupenthixol 1mg per day used to be a popular antidepressant in the UK, it often worked within days. Doses used in psychosis were much higher. It fell out of favour since the SSRIs were launched though, and atypical APs took over. Even low doses of typical APs can cause tardive dyskinesia. This is not likely with risperidone. The Italians use 50mg amisulpride for depression, the effects appear similar to flupenthixol but I guess there's less risk of TD.
The advantage of risperidone over Invega is that it's cheap and very flexible dose-wise. Now that it's licensed for so many different age groups, the 1mg/ml oral solution provides an excellent way to adjust the dose. Assuming you have a generic version like we do here, price is not an issue. The pack is likely to come with a pointless oral syringe which only measures common doses eg. 0.5mg. Throw it away and ask the pharmacist for a proper 1ml syringe. It will either be free (if they're nice) or maybe a dollar or two. Pharmaceutical 1ml oral syringes can measure anything from 0.01ml to 0.99ml, not that you'll need to be that accurate but you get the idea. Not only are they great for awkward doses and awkward children, they can make tapering a breeze. You could start by trying 0.65mg risperidone and see what happens. Don't make any decisions for *at least* a week. You need the drug to reach steady state levels at the very least. If you continue to have libido problems in spite of dose titration, it might be worth seeing what a urologist or endocrinologist has to say. They could measure testosterone etc. to check for any problems.
3. If you decide not to stick with risperidone, would you switch to Invega, or try Abilify? Something similar, or something different?
Abilify is a licensed add-on in resistant depression, it appears to be of moderate utility. It has certainly been widely prescribed in spite of its price tag.
Sexual dysfunction is rare and it never elevates prolactin. Classic EPS movement disorders are uncommon, except perhaps at very high doses. Initial restlessness and nausea are common. Unless the dose is too high, they usually pass. Do not decrease your benzo at this time!
Aripiprazole has a variable effect on bodyweight. If you gave it to someone off the street, it would often cause moderate weight gain. It occurs over time, more slowly than the rapid fat explosions typical of Zyprexa. When added to antipsychotics with strong 5-HT2c antagonism, eg. clozapine, aripiprazole seems to cause weight *loss* and some improvement in metabolic parameters. The same may apply when it's added to olanzapine (Zyprexa). The theory goes that aripiprazole is a partial agonist at 5-HT2c receptors. Compared with placebo, this increased weight, but when it binds in place of a full antagonist (clozapine etc) it reduces weight. Aripiprazole also appears to reduce the risk of weight gain in those treated with mirtazapine, at least in the short-term..... whereas mirtazapine seems to reduce the probability of aripiprazole causing akathisia.
I don't know many people who've taken aripiprazole for OCD or anxiety disorders but I did find this...
Effects of aripiprazole augmentation in treatment-resistant obsessive-compulsive disorder (a double blind clinical trial).
ABSTRACT
BACKGROUND:
Obsessive-compulsive disorder (OCD) is a chronic disorder with unknown etiology. Failure in OCD treatment is common and finding effective augmentations in the treatment of OCD will benefit patients. Antipsychotic augmentation is a common strategy for treatment resistant OCD. This trial evaluated the efficacy of adding aripiprazole in patients whose OCD was insufficiently responsive to an adequate SSRI treatment.
METHODS:
Thirty-nine adult outpatients, who met the DSM-IV-TR criteria for OCD and had treatment resistant OCD were evaluated in a double-blind randomized clinical trial. The patients received either aripiprazole 10 mg/day or placebo, for 12 weeks. Data were analyzed using intention-to-treat analysis with last observation carried forward. All statistical tests were two-sided, and were considered statistically significant at P < 0.05.RESULTS:
A significant reduction in total scores of Y-BOCS (P < 0.0001) was found in the aripiprazole group. Aripiprazole was generally well tolerated. There was no significant difference between the two groups in terms of observed side effects.CONCLUSION:
Results of the present study indicate that aripiprazole could be an effective augmentation medicine in treatment resistant OCD.'If you choose Abilify, I'd go with the manufacturers recommendations for 'augmentation of ADs'. They suggest starting at 2mg or 5mg. If you're rxed 5mg tabs, you could take half a tab for a few days. The usual therapeutic dose seems to be about 5-10mg/day, rarely 15mg. I've not heard of anyone taking more than this for non-psychotic illness. Although low doses of setraline do not interact with Abilify, you can expect some potentiation from 150mg. Be cautious with the Abilify dose.
Abilify has a long half life. Apart from the common practice of using 2mg as a test dose for a couple of days, at least a week should occur between dose increases.
................................................................................
I've looked at your other meds in detail, in an attempt to work out whether any of them might lead to unexpectedly high risperidone/paliperidone levels in spite of your low dose. And to examine the adverse effects of these meds in their own right.
I've searched manufacturer's data sheets (UK and US), pharmacy textbooks, drug interaction textbooks, online journals and psychiatric treatment guides.
Overall, none of your other meds in isolation have a major effect on risperidone or paliperidone blood levels. In combination, there *may* be some effect (small increase), but probably nothing dramatic.
Experts in pharmacokinetics claim that the likelihood of drug interactions increases almost exponentially according to the number of meds in a combination. The reason is that each additional drug may either potentiate the mild enzyme inhibition produced by an existing med or inhibit a different drug metabolising enzyme entirely. On top of this, additive side effects occur whenever drugs acting in similar ways or at the same receptors are Rxed together.
Fortunately, many drugs have more than one means of elimination and so small combos, even involving interacting drugs, are often tolerated reasonably well (except by the elderly or renally impaired!). Large combos can alter so many different aspects of drug metabolism, distribution and elimination that unexpected results may occur.
Even so, none of your existing combo contains any obvious metabolic interactions which would dramatically increase risperidone/paliperidone blood levels.
Sertraline inhibits the enzyme CYP 2D6 mildly at low doses (eg. 50mg) .....but rather strongly at high doses (eg. 150mg). Although risperidone is reliant on this enzyme for conversion to paliperidone, the overall impact of CYP 2D6 inhibitors on the effects of risperidone would not be be expected to be large. This is because paliperidone and risperidone are both active drugs with similar effects. Generally, there would be an increase in the blood level of risperidone, but a corresponding decrease in the level of its active metabolite paliperidone, therefore reducing the impact of this interaction. A small increase in the combined risperidone + paliperidone blood level may occur - mild potential of risperidone's effects would be expected, possibly requiring a small dose reduction. The true interaction, may be more complex, however...
Quite recently, it was discovered that both sertraline and its metabolite act as inhibitors of the well known drug transporter p-GP (p-glycoprotein). p-GP is also called the multi-drug resistance protein. This is because its natural role in the body is to pump drugs out of areas (like the brain) where the body does not expect foreign substances to be present. Certain drugs, such as risperidone and paliperidone, are predominantly removed from the brain by p-GP, thus reducing the concentration of drug available to exert a therapeutic effect.
Studies of various antidepressants and other drugs have shown sertraline to have unexpectedly high potency as a p-GP inhibitor. If sertraline was able to inhibit p-GP in patients, at the blood-brain bariier, it would increase the concentration of risperidone and paliperidone in the brain. This has been demonstrated in mice. Whether it is significant in humans is not known. If it's true, pts on sertraline may require lower risperidone/paliperidone doses than normal.
Anyway, I remember you mentioning a possible decrease in your sertraline dose, perhaps to 100mg? I think this is worthy of further consideration because two drugs associated with sexual/libido issues may be worse than one. Just a thought.
The other enzyme which metabolises risperidone is CYP 3A4. None of your meds inhibit this enzyme, except perhaps to a very minor degree. Buspirone, clonazepam and mirtazapine and all highly dependent on CYP3A4 for their own metabolism, but are not known to inhibit it.
Buspirone is an odd drug. Standard doses, amongst other things, weakly block pre-synaptic D2 receptors. Exceptionally high doses block post-synaptic D2 receptors and can cause antipsychotic-like side effects. Although your dose is high, it isn't *that* high, so I doubt it's potentiating risperidone.
.........................................................................................Only read if you're looking at tapering clonazepam soon.
As you well know, clonazepam can be an difficult med to taper because its exceptionally high potency makes small dose reductions difficult. Personally, I don't think you should even attempt to taper until you've got the Risperdal/Invega situation sorted (hopeful with good success).
But, if you do want to continue tapering in the future, I've written a few tips. I expect you know most of this anyway.
Clonazepam tapers:
Ideally, for anyone with continuing anxiety who has taken benzos for years, tapering will need to be very gradual. The Klonopin 0.125mg wafers are a help but I have a feeling they are not currently in production. I don't know what's going on with the Klonopin brand, Roche are still selling clonazepam in the UK (brand Rivotril). Rivotril 0.5mg are round and quarter scored to facilitate tapering and adjustments, creating an accurate 0.125mg dose is easy. I hear Klonopin 0.5mg tabs have a massive K cut out of the middle. I'm sure this looks 'cool' but it's hardly a help when you need to cut the tablets. Perhaps some of the generics are better designed.
Unfortunately, because clonazepam's water solubility is very poor, it's difficult to use oral syringes as a aid to tapering. Over here, we have a clonazepam oral solution, ideal for tapering. It includes a touch of alcohol (20mg/ml) and some triglycerides to dissolve the clonazepam. Although it's easy to measure with a syringe, regular replacements may be necessary as the alcohol slowly dissolves the numbers on the measuring scale! It's clear that some pharmacists in the US will compound a liquid form if needed. Is this expensive? I assumed it would cost loads but it sounds like it's worth shopping around, if the need arises. I read online that one pharmacy made up a bottle for only $35 using the tablets they'd dispensed for that patient.
Some people go through none of this hassle, however, and find it relatively painless to taper just by cutting the tablets and reducing every few weeks. I think SLS 'bit' little pieces off the tablets at the end of the taper, and had great success with minimal symptoms. It's very individual. If you reach a low dose and find that you can't go any lower without unpleasant symptoms, a switch to a low dose diazepam can be very helpful. The super long half-life of its active metabolite and the low strength scored tablets make tapering in small steps a lot more feasible. A liquid is available if necessary, but it's usually easy to reduce in small steps just by cutting the 2mg tablets. Some clonaz users say diaz makes them tired. I still think diaz is the best benzo ever invented :)
Posted by mogger on October 13, 2014, at 0:39:47
In reply to Re: Sure this problem can be resolved. » mogger, posted by ed_uk2010 on October 12, 2014, at 20:51:46
Ed,
I can't thank you enough for your thoughtful response it is so helpful. You are spot on in that I will not reduce my clonazepam any further until I get the risperdal worked out. Today my depression was better as I believe that it takes me about 2.5 weeks to properly adjust to an 1/8th of a decreased dose of clonazepam as I have been on it for about 7 years. My doctor and I always do one thing at a time but we did decrease my risperdal 10 days ago so I believe it could have been a double whammy adjusting to the decrease in both medications.
I had an initial AD response to Latuda but akathisia kicked in even below sub therapeutic doses. My doctor has told me that in his experience he knows of abilify and clozapine to be the only two APs that can exacerbate OCD. My sister was put on Abilify and it manifested OCD in her. Not to say that would happen to me but the nice thing is that the risperdal really cuts into my OCD thoughts.
I think you are right about trying a decrease in sertraline as even before adding risperdal I can think of some decreased libido but the risperdal has definitely made it worse. I forgot to tell you that I take inositol for ocd and I remember it having an added negative effect on my libido. As you say all of these things added together perhaps is what is happening. I feel relieved that my prolactin is normal so I don't have to go off risperdal immediately.
My insurance is excellent at the moment so Invega would not cost much so that could be an option. Are you aware of any emotional differences between the two medications? Meaning does one tend to cause anhedonia or emotional blunting more than another at similar doses? I know this is impossible to answer unless I try it.
On a side note I can easily take a .5mg tablet and a half of a .25mg tablet so it would be in between .5 and .75mg to see if that is a optimal dose. I shall hang here for another week just to take a breather and then try tackling what you have discussed.
Many thanks again Ed for your thorough response. I have read everything a few times.
mogger
Posted by ed_uk2010 on October 13, 2014, at 20:43:24
In reply to Re: Sure this problem can be resolved. » ed_uk2010, posted by mogger on October 13, 2014, at 0:39:47
Hi Joseph,
>I can't thank you enough for your thoughtful response it is so helpful.
You're welcome.
>You are spot on in that I will not reduce my clonazepam any further until I get the risperdal worked out.
Definitely, that's very important.
>I believe it could have been a double whammy adjusting to the decrease in both medications.
It could indeed. Maybe stay on 0.5mg Risperdal for a bit longer in case the response improves once you're adjusted to your lower clonazepam dose.
>I had an initial AD response to Latuda but akathisia kicked in even below sub therapeutic doses.
Latuda causes akathisia about as often as some typical APs eg. Thorazine at full neuroleptic doses. I don't think they should have been able to market it as 'atypical' because that suggests low EPS risk, at least at standard doses.
Drug regulation is odd. Some countries refused to allow amisulpiride to be classed as an atypical because it doesn't block serotonin 5-HT2 receptors. I expect this is why it was never marketed in the US. Personally, I don't think blocking 5-HT2 receptors is a good definition of atypical... neither is increased efficacy, some atypicals have no evidence of superior efficacy. Some even seen less effective. The atypicals are a diverse group, some elevate prolactin, some don't, some are very sedating, some aren't etc. The only think they have in common is that they all cause less acute EPS than standard-high dose haloperidol and usually considerably less than other typicals such as chlorpromazine (Thorazine). According to a meta-analysis, Latuda produces a similar incidence of acute EPS to Thorazine. It also causes more EPS than Risperdal, despite the high Risperdal doses used in early trials. Amisulpride, which some countries refused to call an atypical, causes fewer EPS than Latuda.
>My doctor has told me that in his experience he knows of abilify and clozapine to be the only two APs that can exacerbate OCD.
Well, that's his experience, but aggravation of OCD has certainly been reported with other APs, as has improvement. In schizophrenia, there are many reports of OCD-like illness appearing on clozapine, but there are also a lot of reports for olanzapine (Zyprexa) and a few for risperidone (Risperdal)!
In non-psychotic pts, various APs have been used as an 'add on' to SSRIs in OCD. There is more evidence here to support the usefulness of risperidone than the others. There's a bit of evidence to support aripiprazole but the studies are very small.
Clozapine or olanzapine + frequent OCD symptoms in schizophrenia.
http://www.ncbi.nlm.nih.gov/pubmed/25256097
.............................
http://www.ncbi.nlm.nih.gov/pubmed/25268790
In the above study, albeit small, scientists tried to find differences in brain functioning between schizophenics given clozapine or olanzapine, Group 1.....and those given amisulpride or aripiprazole, Group 2. As expected, more OCD-like symptoms were seen with clozapine and olanzapine, and it seems to correlate with differences in localised brain activation between the groups.
Allegedly, in four patients, aripiprazole reversed the OCD symptoms cause by clozapine....
http://www.ncbi.nlm.nih.gov/pubmed/24330737
A similar case report described a marked improvement in OCD when aripiprazole was added to the regimen of a schizophrenic pt on olanzapine.
>My sister was put on Abilify and it manifested OCD in her. Not to say that would happen to me but the nice thing is that the risperdal really cuts into my OCD thoughts.
Well, it's a bit concerning, but I wouldn't rule out Abilify of this basis, just go easy on the dose.
>I think you are right about trying a decrease in sertraline as even before adding risperdal I can think of some decreased libido
Do you think you doc might agree to try something along the lines of 125mg for a couple of months then 100mg? But should you start this now or adjust Risperdal first? It might be easier to adjust Risperdal first because the effects/side effects due to Risperdal dose changes are more rapidly assessed. And then there's the whole confusion of adjusting more than on med at once.
>I forgot to tell you that I take inositol for ocd and I remember it having an added negative effect on my libido.
Does it help and will you continue it?
>I feel relieved that my prolactin is normal so I don't have to go off risperdal immediately.
You wouldn't anyway. Drug-induced prolactin elevation is not an emergency, even if the elevation is pretty extreme.
>Are you aware of any emotional differences between the two medications? Meaning does one tend to cause anhedonia or emotional blunting more than another at similar doses?
No, not especially.
>On a side note I can easily take a .5mg tablet and a half of a .25mg tablet so it would be in between .5 and .75mg to see if that is a optimal dose.
Good idea. I forgot about the 0.25mg tablets because they don't sell them here.
>I shall hang here for another week just to take a breather and then try tackling what you have discussed.
Good. If you still feel some depression and anxiety, maybe add the half a 0.25mg risperidone to your current dose.
Best of luck. Let us know how you do.
Posted by mogger on October 15, 2014, at 23:31:34
In reply to Re: Sure this problem can be resolved. » mogger, posted by ed_uk2010 on October 12, 2014, at 20:51:46
Thanks Ed I shall see my pdoc actually on friday. I went up to .625mgs of risperdal (in between doses as you mentioned) last night and slept better and can already feel more calm.
I have a quick question for you if you don't mind. How quickly do you think it is a good idea to taper off clonazepam after I have been on it for 7 years? My pdoc said 1/8th of a dose per week but I have heard that sometimes it should be 1/8th of dose every two weeks? I went down from 1mg to .5mg in four weeks (1/4 tablet per week) and then stopped tapering as we discussed. It has now been almost 3 weeks since stopping the taper at .5mg but I am wondering to myself if I am still having withdrawals from clonazepam if I in fact tapered too quickly? Penny for your thoughts,
mogger
Posted by mogger on October 17, 2014, at 18:08:17
In reply to Re: Sure this problem can be resolved. » ed_uk2010, posted by mogger on October 15, 2014, at 23:31:34
One more thing Ed sorry for all the questions. I saw my pdoc today and we are going back up to .75mg of risperdal because even at .625mg my depression has returned. As my prolactin was in the normal range (top 1/3rd of the normal range though) and I had been at .75mgs of risperdal for 2 months, dose prolactin levels keep rising with risperdal or do you think after 2 months my prolactin level had leveled off and wouldn't go higher? Thanks Ed,
Mogger
Posted by ed_uk2010 on October 18, 2014, at 22:34:35
In reply to Re: Sure this problem can be resolved. » mogger, posted by mogger on October 17, 2014, at 18:08:17
>Do prolactin levels keep rising with risperdal or do you think after 2 months my prolactin level had leveled off and wouldn't go higher? Thanks Ed
After two months on a stable dose, I would not expect it to get any higher. It would not be identical if you had it re-measured however, because levels can vary according to the time of day, tending to be highest in the early morning. Brief rises can be seen after meals and physical activity.
Posted by mogger on October 18, 2014, at 23:39:08
In reply to Re: Sure this problem can be resolved. » mogger, posted by ed_uk2010 on October 18, 2014, at 22:34:35
Thanks Ed. I hope that if I need to go to 1mg of Risperdal at some point that such an increase from .75mg to 1mg won't have a massive spike in prolactin but who knows. Hope you are well and thanks again for your responses,
mogger
Posted by ed_uk2010 on October 21, 2014, at 22:03:13
In reply to Re: Sure this problem can be resolved. » ed_uk2010, posted by mogger on October 18, 2014, at 23:39:08
You're welcome. I'm in the process of formulating a reply..
Posted by ed_uk2010 on October 27, 2014, at 17:52:29
In reply to Re: Sure this problem can be resolved. » ed_uk2010, posted by mogger on October 18, 2014, at 23:39:08
Hi J,
Really sorry for the lack of the reply I promised. Various circumstances have meant I've not been able to go on babble for a few days.
I've got a half-written message for you saved on my computer.
Anyway, hope you're doing OK :)
Please will you let me know your current symptoms/side effects, meds/doses + any other relevant info. I may need to amend the reply I wrote earlier if things have changed.
Thanks and take care.
This is the end of the thread.
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