Raku: Benzo / Olanzapine withdrawal, advice needed to stabilise, Thanks!

[raku]

Hi everybody, 

 

I am writing this post on behalf of my wife. Due to some possible withdrawal symptoms such as blurred vision and intense fatigue/drowsiness, my wife is currently unable to post herself.

 

My wife was admitted to hospital in Jan 2023 for her first psychotic episode. During her stay in hospital, she took four anti-psychotic drugs (Olanzapine, Blonanserin, Haplodil Injection, Quetiapine) and three Benzodiazepines (Clonazepam, Brotizolam, Nitrazepam). A mix of up to seven psychotropic drugs kept my wife in bed all day. The psychiatrist here masks the side effects of antipsychotics such as Akathisia, Restless Legs and Drug-induced Parkinsonism by over-sedating and drowsiness. When she was discharged in February, she continued to take 10mg Olanzapine, 2mg Biperiden* as well as two Benzodiazepines (1mg Clonazepam and 0.25mg Brotizolam**).

 

I found this forum because I am doing my best to help my wife get off (or reduce as much as possible) the psychotropic drugs she is currently taking. I cannot trust the Japanese psychiatrists who are so keen to use multiple benzodiazepines at the same time, and it is desperate that these drugs are even used just to prevent insomnia even though my wife doesn't have it.

 

Since being discharged from hospital in Feb 22, we have been tapering the dose of Brotizolam and Clonazepam out of fear of using multiple benzodiazepines at the same time. We would like to stop the Brotizolam but keep the low dose of Clonazepam and wait for the status to stabilize before starting the Olanzapine taper.

 

From March to April this year, the dose of Brotizolam was reduced from 0.25mg to 0.0625mg, the dose of Clonazepam was reduced from 1mg to 0.5mg and Olanzapine was always 10mg.

On April 21, my wife's daily medication and supplements were as follows:

10:00 Vit C 250mg, Vit B-Complex***, Ginkgo biloba 60mg

13:00 Vit C 250mg, Vit B-Complex, Ginkgo biloba 60mg

18:30 Biperiden 1mg, Clonazepam 0.5mg, Vit E 400IU, Omega-3 1000mg

20:00 Olanzapine 10mg, Brotizolam 0.0625mg

 

At that time, she was in a more stable state and although she had some symptoms of side effects of the medication, such as blurred vision, lack of concentration and poor short-term memory, they were all at an acceptable level and she was able to do simple light exercise every day.

 

However, after this she experienced problems. From April 22 my wife stopped taking Brotizolam and reduced the dose of Biperiden from 1mg to 0.5mg on April 28.

From April 28 till now, my wife's daily medication and supplements were as follows:

10:00 Vit C 250mg, Vit B-Complex, Ginkgo biloba 60mg

13:00 Vit C 250mg, Vit B-Complex, Ginkgo biloba 60mg

18:30 Biperiden 0.5mg, Clonazepam 0.5mg, Vit E 400IU, Omega-3 1000mg

20:00 Olanzapine 10mg

 

Those days, April 24-30, were supposed to be her best days since her discharge from hospital. However, the situation began to turn bad on May 2 when she started to become extremely fatigued and drowsy. She goes to bed at 20:00 and struggles to get up at 10:00. Even after 13-14 hours of sleep she still felt tired, had no interest or motivation to do anything even talk to our children, and wanted to lie down during the day except to eat even though she could not fall asleep. It is usually at 17:00 that her energy returns a little and she gets up for dinner. She did not have insomnia at night but would have vivid dreams could describe the details of them when she woke up, sleep did not seem to give her brain any real rest. Although I kept holding her hands and hugging her to comfort her as much as possible, she felt overwhelmed with failure and powerlessness, she became very depressed and felt like a wreck, she was worried that her state would not improve and she was worried that she would not be able to return to work in 1 month (her sick leave was due to end in a month). This state of extreme fatigue continues to this day and the only good news is that apart from the fatigue she does not seem to have any other new noticeable withdrawal symptoms.

 

Biperiden does not seem to have serious withdrawal symptoms (correct me if I'm wrong), it is anticholinergic medication that works to alleviate the Drug-induced Parkinsonism caused by Olanzapine, which were barely felt on the previous few dose reductions. Personally, we tend to think that it is mainly the withdrawal of Brotizolam that causes the intense fatigue, and that several Brotizolam reductions at the end of March similarly caused fatigue(slightly lighter than now), but it goes away after 2 days.

 

Current questions:

1. Should I keep the status and be patient and wait for the withdrawal symptoms to go away? Still have 1 month of sick leave left.

2. Today is day 13 after Brotizolam withdrawal and day 4 of intense fatigue/drowsiness. If after 1 week there is still no improvement in status, should the dose of Brotizolam be resumed to 0.0625mg? or is it better to be resumed now?

3. Are there ways to reduce vivid dreams and improve the quality of sleep?

4. If Brotizolam is not resumed, what non-pharmacological methods are available to alleviate withdrawal symptom? I have searched and read some of the posts in the forum but they seem to be mainly for insomnia and anxiety, are there any methods and suggestions for fatigue relief?

 

I wish I had found this place earlier, after reading some of the posts I realized that the Brotizolam was being tapered too quickly and that this was causing my wife's withdrawal symptoms. But it's all happened and it's no use regretting it and hopefully I can get some advice and help here to get things back on track from now on.

 

A little help and advice would be great. Thank you for your help in advance!

 

---------------------------

*Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease and certain drug-induced movement disorders. It is not recommended for tardive dyskinesias. Common side effects include blurred vision, dry mouth, sleepiness, constipation, and confusion. It should not be used in people with a bowel obstruction or glaucoma. Biperiden is in the anticholinergic family of medication. (From Wiki https://en.wikipedia.org/wiki/Biperiden)

 

**Brotizolam, (marketed under brand name Lendormin) is a sedative-hypnotic thienotriazolodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to other short-acting hypnotic benzodiazepines such as triazolam or midazolam. It is used in the short-term treatment of severe insomnia. Brotizolam is a highly potent and short-acting hypnotic, with a typical dose ranging from 0.125 to 0.25 milligrams, which is rapidly eliminated with an average half-life of 4.4 hours (range 3.6–7.9 hours). (From Wiki https://en.wikipedia.org/wiki/Brotizolam)

 

***Vit B-Complex = B1 20mg, B2 15 mg, B6 15 mg, B12 10mcg, Niacin 20mg, Pantothenic Acid 20mg, Biotin 25mcg, Folate 100mcg, Inositol 25mg

 

 

[Altostrata]

Welcome, @raku

 

Your wife's situation is about as complicated as they can get. Please stop dosage changes while we sort this. What times o'clock does she take her drugs, with dosages? Are her symptoms better or worse at any particular times of day?

[FireflyFyte]

Your wife is very lucky to have you as a support during all of this and am sure the moderators on this site can provide trusted guidance on how to proceed minimizing her drug cocktail.

[raku]

Hi, @Altostrata

Thank you for your response and warm welcome.

 

We will not adjust the dose until the situation is stable.

Since 28 April, my wife has been taking the following drugs schedule and dose:

18:30 Biperiden 0.5mg, Clonazepam 0.5mg

20:00 Olanzapine 10mg

 

She usually doesn't regain some strength and energy until 17:00 to 18:30, and mostly feels fatigued the rest of the time.

This is her recent routine:

9:00, Wake up, in April she can usually get up at 7:30.

9:30, Breakfast

10:00, Supplements Vit C 250mg, Vit B-Complex***, Ginkgo biloba 60mg

10:00-12:00, If her energy allows, she watches or listens to YouTube programmes. Simple housework or walking downstairs can make her tired and have to go to bed.

12:00, Lunch

12:30, Supplements Vit C 250mg, Vit B-Complex***, Ginkgo biloba 60mg

13:00-17:00, Fatigue, lethargy. Usually rests in bed, but does not always fall asleep. She describes being in a half-asleep state.

17:00, Some energy restored, get up

17:30, Dinner

18:00-18:30, Walk outside

18:30, Biperiden 0.5mg, Clonazepam 0.5mg

20:00, Olanzapine 10mg

20:00, Sleep, no insomnia, but lots of vivid dreams. At 1:00 usually get up once during the night to go to the toilet and can go back to bed and fall back asleep.

 

I find it strange why stopping Brotizolam would cause fatigue. The insomnia that would normally result did not happen instead. I think maybe it's because the sedative effect of Olanzapine is already so strong that it masks the withdrawal insomnia of Brotizolam. My wife could fall asleep but the quality of sleep was significantly reduced.

 

Also, my previous knowledge of Biperiden (an antiacetylcholine drug) may have been inadequate. I have done some brief literature searches over the past few days and have come up with 3 pieces of information that may be helpful.

1. antiacetylcholine drugs reduce REM sleep and taper off leads to an increase in REM sleep.

2. antiacetylcholine drugs increase dopamine concentrations in the brain and act as potent indirect dopamine agonists.

3. withdrawal symptoms of EPS and those of cholinergic rebound may reach their peak within 2 weeks after abrupt discontinuation of anticholinergics.

 

Quote

Despite the controversy over the importance of cholinergic regulation on REM sleep, multiple lines of in vivo pharmacological evidence consistently indicated muscarinic acetylcholine receptors are important for REM sleep regulation. Muscarinic receptor agonists and acetylcholinesterase inhibitors increase REM sleep and shorten the REM latency (the time-delay of REM start after the NREM start). On the other hand, muscarinic receptor antagonist decreased REM sleep and lengthened the REM latency.

(From Molecular Mechanisms of REM Sleep, https://www.frontiersin.org/articles/10.3389/fnins.2019.01402/full)

 

Quote

Anticholinergic antiparkinson agents prolong dopamine action in the brain by inhibiting the reabsorption and storage of neurotransmitters. Reabsorption is a normal mechanism by which the body controls how long a nerve signal lasts. However, reabsorption can be an issue when there is a low level of dopamine. Hence, by limiting the reuptake of dopamine, anticholinergics increase dopamine concentration in the brain.

(From HOW DO ANTICHOLINERGIC ANTIPARKINSON AGENTS WORK? https://www.rxlist.com/how_do_anticholinergic_antiparkinson_agents_work/drug-class.htm)

 

Quote

Antipsychotic drugs can reduce dopaminergic activity through the blockade of dopamine D2 receptors and alter this balance, thereby producing EPS. Currently available antiparkinsonian anticholinergic drugs (e.g. benztropine, biperiden, and trihexyphenidyl) can block excitatory cholinergic pathways in the basal ganglia and restore the dopamine/acetylcholine balance. The antimuscarinic, rather than antinicotinic, properties of anticholinergics are thought to be responsible for their efficacy in treating EPS. Antiparkinsonian anticholinergics generally block all subtypes of mAChR, but most of them show the highest affinity for M1 receptors. The difference in optimal-dose level between the different anticholinergics appears to be associated with their relative potency in binding to mAChR. Anticholinergic drugs also act as potent indirect dopamine agonists by blocking the presynaptic uptake of dopamine and causing its release from presynaptic terminals. In addition, they strongly inhibit the presynaptic reuptake of norepinephrine and weakly inhibit the reuptake of serotonin.

Quote

Many authors have reported that the use of anticholinergics in schizophrenia is associated with decreases in cognitive function, including memory, learning, attention, and executive function.

Furthermore, discontinuing biperiden use significantly improved subjective QOL and psychiatric symptoms without significant adverse effects. It has been reported that withdrawal symptoms of EPS and those of cholinergic rebound may reach their peak within 2 weeks after abrupt discontinuation of anticholinergics. In our study, biperiden was reduced at a rate of 1 mg/2–4 weeks, which may be a safe strategy for discontinuation of long-term biperiden use in schizophrenia. It also appears to be important to taper biperiden over at least 4 weeks.

(From: Benefits and limits of anticholinergic use in schizophrenia: Focusing on its effect on cognitive function, https://onlinelibrary.wiley.com/doi/full/10.1111/pcn.12088)

 

 

[raku]

Hi @FireflyFyte

Thank you for your reply.

 

I feel so lucky to have found this place, if I had come here earlier this might have made everything less difficult. Cocktail therapy is horrible and due to the Covid-19 control measures in Japan at the beginning of this year I could not even visit my wife while she was in hospital and I did not know about the drugs she was using until she was discharged. I have applied for a 1 year break from work and I have to take care of my wife and 3 year old child. I believe that eventually time and love will heal everything, but of course it needs to be done the right way.

[Altostrata]

The combination of drugs that she's taking would make anyone tired.

 

Which symptoms do you think are withdrawal symptoms?

[raku]

1 hour ago, Altostrata said:

The combination of drugs that she's taking would make anyone tired.

 

Which symptoms do you think are withdrawal symptoms?

 

Thank you very much for your reply.

 

To be honest, we don't know how to differentiate between withdrawal symptoms or side effects of the drugs. If you could give even a little bit of advice that would be great. Thanks in advance.

 

These are the main symptoms that my wife currently has:
Intense fatigue (since May)
Drowsiness, trying to sleep all the time, before 4pm (since May)
Poor concentration
Blurred vision with superimposed shadows
Poor short-term memory
No facial expression
Slow movements

Slight, involuntary tremor of the arms and legs, appearing as a single tremor or spasm, which is irregular and not continuous.

 

No new symptoms of discomfort, other than fatigue and drowsiness, have occurred since May. We tend to think of fatigue and drowsiness as a withdrawal symptom simply because this did not occur throughout March to April. And at the end of April, my wife stopped the Brotizolam and reduced Biperiden. In fact, there seems to be some improvement in other areas of my wife's condition, including short-term memory, vision and short-term concentration.

 

By the way, we saw a new psychiatrist today who could understand English but would only express himself in Japanese. It's hard to find an English speaking doctor in Japan, let alone a psychiatrist.

Some points from him:
1. Fatigue and sleepiness are more like side effects of the drug rather than withdrawal symptoms.
2. Resumption of Brotizolam is not recommended unless the quality of sleep deteriorates further. Although he does not think it is wise to stop taking sleeping pills.
3. It is recommended that Biperiden be restored to 1mg, which is a very small dose. This will reduce the muscle tone problems associated with Olanzapine and will be of some help in improving exercise capacity. However, it is theoretically detrimental to memory and eyesight. The dose of Biperiden will be lowered later when the dose of Olanzapine is reduced somewhat.

 

This psychiatrist may not understand withdrawal symptoms, but at least he seemed willing to listen to us and could get us to communicate in English. 

Of course, we did not adjust the dose of any drugs, including Biperiden.

 

[Altostrata]

On 5/18/2023 at 9:42 PM, raku said:

1. Fatigue and sleepiness are more like side effects of the drug rather than withdrawal symptoms.

 

I agree with this. I do not see withdrawal symptoms in the symptom pattern you reported. She is taking a lot of drugs.

 

Any change in symptom pattern since you decreased on April 28?

 

On 5/5/2023 at 2:26 PM, raku said:

The psychiatrist here masks the side effects of antipsychotics such as Akathisia, Restless Legs and Drug-induced Parkinsonism by over-sedating and drowsiness.

 

Did your wife have these adverse effects in the hospital? 

 

On 5/18/2023 at 9:42 PM, raku said:

3. It is recommended that Biperiden be restored to 1mg, which is a very small dose. This will reduce the muscle tone problems associated with Olanzapine and will be of some help in improving exercise capacity. However, it is theoretically detrimental to memory and eyesight. The dose of Biperiden will be lowered later when the dose of Olanzapine is reduced somewhat.

 

What about lowering the olanzapine dose instead?

[raku]

2 hours ago, Altostrata said:

I agree with this. I do not see withdrawal symptoms in the symptom pattern you reported. She is taking a lot of drugs.

 

Any change in symptom pattern since you decreased on April 28?

 

Hi Alto, Thank you so much for your reply.

 

My wife's symptoms have improved a little, but not much. She spent less time in bed in the afternoons but still felt fatigued and lethargic most of the day. Over the past week we have tried taking Olanzapine half an hour earlier and she now seems to be able to get up half an hour earlier in the morning accordingly.

 

2 hours ago, Altostrata said:

On 5/5/2023 at 9:26 PM, raku said:

The psychiatrist here masks the side effects of antipsychotics such as Akathisia, Restless Legs and Drug-induced Parkinsonism by over-sedating and drowsiness.

Did your wife have these adverse effects in the hospital? 

 

Yes, especially Restless Legs and Drug-induced Parkinsonism.

 

 

2 hours ago, Altostrata said:

What about lowering the olanzapine dose instead?

 

The psychiatrist recommend maintaining the olanzapine dose of 10mg until the end of July, and then will try to lower the dose to 7.5 mg.

 

[Altostrata]

Since your wife does not seem to have withdrawal symptoms and may be at risk for serious adverse effects of olanzapine, such as a movement disorder, if I were you, I might stop reducing biperiden and start reducing olanzapine in the near future -- unless you think her present state is therapeutic for her.

 

For your information Tips for tapering off olanzapine (Zyprexa)

[FireflyFyte]

1 hour ago, raku said:

The psychiatrist recommend maintaining the olanzapine dose of 10mg until the end of July, and then will try to lower the dose to 7.5 mg.

 

I wouldn't make a straight jump from 10mg -> 7.5mg as it's a 25% drop and could trigger withdrawal symptoms. I would recommend dropping by 10% per month (so first drop would be to 9mg) or 5% every two weeks (first drop would be to 9.5mg).

[raku]

5 hours ago, Altostrata said:

Since your wife does not seem to have withdrawal symptoms and may be at risk for serious adverse effects of olanzapine, such as a movement disorder, if I were you, I might stop reducing biperiden and start reducing olanzapine in the near future -- unless you think her present state is therapeutic for her.

 

For your information Tips for tapering off olanzapine (Zyprexa)

 

Thanks for your advice. 

I read the Tips for Tapering off olanzapine carefully and I will make some preparations, such as buying a digital scale. I think we will start the olanzapine tapering on 1 June.

 

 

4 hours ago, FireflyFyte said:

 

I wouldn't make a straight jump from 10mg -> 7.5mg as it's a 25% drop and could trigger withdrawal symptoms. I would recommend dropping by 10% per month (so first drop would be to 9mg) or 5% every two weeks (first drop would be to 9.5mg).

 

Yes, you are right, I think so too. In fact, my wife had already tried the 7.5mg dose during her hospital stay in February. But at that time the psychiatrist thought she was showing signs of relapse.

Now that I think about it, maybe that was more like withdrawal symptoms, after all, the process of going from cocktail therapy to 7.5mg of olanzapine alone in 1 month was too quick.

 

By the way. I was so happy for you when I learned that you had tapered your olanzapine dose to 1.56mg.

 

[FireflyFyte]

12 hours ago, raku said:

Yes, you are right, I think so too. In fact, my wife had already tried the 7.5mg dose during her hospital stay in February. But at that time the psychiatrist thought she was showing signs of relapse.

Now that I think about it, maybe that was more like withdrawal symptoms, after all, the process of going from cocktail therapy to 7.5mg of olanzapine alone in 1 month was too quick.

 

It seems to be fairly common to label withdrawals as relapse/return of symptoms.

 

12 hours ago, raku said:

By the way. I was so happy for you when I learned that you had tapered your olanzapine dose to 1.56mg.

 

Thank you 💜 I have been tapering 5% every two weeks and haven't suffered any noticeable withdrawals to date.

[Altostrata]

Using a liquid to taper is much easier than using scales to weigh the drug.

[JandD]

Dear Raku,
I wish you much strength and a positive course of health for your wife. I was or am in a similar situation as you. It is very good that you are in this forum and that you are very well informed. This way you can avoid mistakes. You have people here with a lot of experience, excellent knowledge and positive intentions. This way you can better assess which course of action is good for your wife and which decisions of psychiatrists should be questioned very critically under certain circumstances. For us, a careful reduction that does not overburden my wife was very important. We also follow a holistic approach. So, step by step, within a year, we have managed to live a mostly normal everyday life again. 

Positive things for us:

• Diary: We use a spreadsheet and record how the sleep was, what happened that day, what physical and mental sympthoms my wife had, what supplements she took and exactly what the status of the reduction of medication is. This way you can see which things have positive or negative effects. 
• Food supplements: Every person reacts differently. I find the information from the Walsh Research Institute interesting. You might want to have your blood tested. My wife benefits from B vitamins (B6), zinc, vitamin C, fish oil and magnesium. Vitamin E and grape seed against side effects of Olanzapine. We no longer take NAC.
• Do everything gently. Make small adjustments. In tapering, but also supplementing food.
• Time spacing of medications due to metabolisation. For us, 8pm Olanzapine, about 10:30pm Mirtazapine.
• Fresh air, exercise, sunshine and as regular a day as possible.
• Avoid stress, pressure or triggers if possible.
• Everyday life and nice things, such as walks, travel reports, music.
• A weight blanket reduced anxiety.
• Healthy diet. Little sugar, wheat, processed food. No caffeine or sweeteners. Probiotics from time to time. Good gut flora is important and unfortunately negatively affected by medication.
• A reduction by liquid (scales too inaccurate). Here, one part solid (e.g. 7.5mg) and one part liquid (2.5mg). Reduce the liquid part slowly by pipette.
• Tapering step by step. We currently reduce 7.5-15% per month, depending on my wife's condition. The reduction is done in small steps over about 10 days. Then there is a break of 20 days so that the brain can adjust.
• Adjusting the reduction to menstruation. My wife usually feels a little worse before and during this time. We therefore always start the reduction shortly after this time and then take the approx. 20-day break.
• Every few months we take a slightly longer reduction break to give the brain more time to adjust. The slow way often seems to me to be the faster way in the end.
• Think and take care of yourself and enjoy the time with your son. It all takes time and it is important that you are doing well!

I think we will stay in touch ;-)

[PortugueseSea]

Dear Raku,

As a fellow resident in Japan, I have read your Intro with interest.

I hope your wife is making a smooth recovery.

These syndromes can be extremely hard on people. She is lucky to have such a supportive husband!