Tips for tapering off clomipramine (Anafranil)

[Altostrata]

Clomipramine is an older tricyclic antidepressant like amitriptyline and nortriptyline. It is a chemical derivative or analog of another TCA, imipramine. Of the TCAs, imipramine and clomipramine are the most potent serotonin reuptake inhibitors.

 

About clomipramine, from official US FDA information at dailymed.nlm.nih.gov:

 

Quote

Initial Treatment/Dose Adjustment (Adults)

Treatment with clomipramine HCl capsules, USP should be initiated at a dosage of 25 mg daily and gradually increased, as tolerated, to approximately 100 mg during the first 2 weeks. During initial titration, clomipramine HCl capsules, USP should be given in divided doses with meals to reduce gastrointestinal side effects. Thereafter, the dosage may be increased gradually over the next several weeks, up to a maximum of 250 mg daily. After titration, the total daily dose may be given once daily at bedtime to minimize daytime sedation.

 

Initial Treatment/Dose Adjustment (Adults)

Treatment with clomipramine HCl capsules, USP should be initiated at a dosage of 25 mg daily and gradually increased, as tolerated, to approximately 100 mg during the first 2 weeks. During initial titration, clomipramine HCl capsules, USP should be given in divided doses with meals to reduce gastrointestinal side effects. Thereafter, the dosage may be increased gradually over the next several weeks, up to a maximum of 250 mg daily. After titration, the total daily dose may be given once daily at bedtime to minimize daytime sedation.

....

Withdrawal Symptoms

A variety of withdrawal symptoms have been reported in association with abrupt discontinuation of clomipramine HCl, including dizziness, nausea, vomiting, headache, malaise, sleep disturbance, hyperthermia, and irritability. In addition, such patients may experience a worsening of psychiatric status. While the withdrawal effects of clomipramine HCl have not been systematically evaluated in controlled trials, they are well known with closely related tricyclic antidepressants, and it is recommended that the dosage be tapered gradually and the patient monitored carefully during discontinuation.

 

Clomipramine is metabolized via liver enzymes P450 CYP2D6 and 3A4 (it is a CYP1A2 inhibitor) ; it may conflict with other drugs utilizing those liver enzymes. The drug is prescribed with warnings about interaction with fruit juices such as grapefruit juice or cranberry juice.

 

With its active metabolite, desmethylclomipramine (DMI) or norclomipramine, clomipramine has a long half-life of about 54-77 hours.

 

From US FDA information at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1739aa5-69d8-4a69-be58-6d789ea2a516

Quote

Because both CMI and its active metabolite, DMI, have long elimination half-lives, the prescriber should take into consideration the fact that steady-state plasma levels may not be achieved until 2 to 3 weeks after dosage change.... Therefore, after initial titration, it may be appropriate to wait 2 to 3 weeks between further dosage adjustments.

 

Brand-name Anafranil and generic clomipramine are supplied in 25 mg, 50 mg, 75 mg capsules. Generics may also be available in 10mg, 25mg, 50mg tablets.

 

Clomipramine may also be available in sustained-released (SR) tablets.

 

Reduce by 10% per month to start

The 10% rule holds for clomipramine, just like other psychiatric drugs: Reduce by 10% per month, calculated on the last dosage. (The amount of the reduction gets progressively smaller.)

 

See Why taper by 10% of my dosage?

 

Use a combination of clomipramine dosages to taper

If you are taking, for example, 150mg, you may wish to get 50mg of your prescription in 10mg tablets (if available). This will enable you to decrease by 10mg at a time.

 

(To justify a prescription comprised of various dosage capsules or tablets for insurance coverage, your doctor may need to indicate split dosing -- taking the drug more than once a day.)

 

When you are down to 100mg, you may wish to have your prescription filled with 50mg capsules or tablets plus 10mg tablets and carefully split the tablets until you are down to 50mg.

 

The smallest decrease you can make with available tablet sizes would be 2.5mg -- 1/4 of a 10mg tablet. Accurately cutting a tablet into quarters can be difficult. When you need to make a decrease smaller than 5mg (half a 10mg tablet), you may wish to to cut up tablets, weigh the powder (from the capsules), get a prescription for the liquid, or make a liquid to continue a 10% taper.

 

At 50mg and lower, you may wish to combine whole 25mg capsules or tablets with partial tablets or powder from the capsule weighed for accuracy, or a liquid to fill out the rest of your daily dose.

Also see Combining tablets or capsules with liquid to taper

 

Make a clomipramine liquid yourself from tablets or capsules

The immediate-release form of clomipramine is freely soluble in water (pdf). (The sustained-release tablets (SR) cannot be dissolved in water, they will need to be split or weighed for tapering.)

 

Making a liquid from the immediate-release tablets is quite easy. See How to make a liquid from tablets or capsules

 

Use an oral syringe to precisely measure out doses as small as 0.01mg.

 

From The Canadian Journal of Hospital Pharmacy — Volume 42, No. 6, December, 1989 Page 248

Quote

 

Clomipramine Suspension Formulations

 

Clomipramine is a tertiary tricyclic amine with antidepressant properties. It is commonly used in psychiatry to treat depression, panic attacks, phobias and obsessive-compulsive disorders, The parent drug affects serotonin uptake, while the active desmethyl metabolite has a more predominant effect on nor-adrenaline uptake.

As a result of these many indications, the pharmacy department at the Children’s Hospital of Eastern Ontario receives requests to prepare clomipramine suspension. A literature review resulted in no stability data for a liquid preparation, yet a formulation was found in one reference.1

Clomipramine suspension (5mg/mL) was prepared according to two different formulations. The first product was compounded using simple syrup B.P. as the suspending agent. The second formulation was prepared using the Hospital for Sick Children (HSC) suspension vehicle.2 Aliquots from both batches of suspension were analyzed by a stability-indicating gas chromatographic method in the quality control laboratories of Ciba-Geigy Canada. Samples were analyzed on day zero and then stored at 10°C for 30 days and re-analyzed. The results on day zero were 3.9 mg/g for both suspensions. (Results are expressed on a weight/weight basis because of the viscous nature of the suspension.) Day 30 results were 3.6 mg/g and 3.5 mg/g for the HSC and simple syrup suspensions respectively.There were no secondary degradation products in any of the samples. Samples were also sent for micro-
biological testing. After 10 days incubation there was no bacterial growth for either product.

Based on these results, the two formulations of clomipramine suspension (5 mg/mL) were determined to be chemically stable for up to 30 days when stored under refrigeration and protected from light.

Colline Blanchard, B.Sc.Pharm.
Senior Pharmacist
Children's Hospital of Eastern Ontario
Ottawa, Ontario

Ron Donnelly, B.Sc.Pharm.
Product Development Pharmacist
Ottawa Civic Hospital
Ottawa, Ontario

 

Here is a recipe for a clomipramine suspension from Alberta Health Services (2016). Note it says

Quote

Simple Syrup can be used instead of HSC vehicle.

 

Have a compounding pharmacy make custom capsules or a liquid
Compounding pharmacies can make capsules with custom dosages or a liquid from the powder. You will need a prescription written for any  compounding. The only drawback is insurance may not cover it; it can be quite expensive.

 

About the sustained-release form
Sustained-release clomipramine tablets (SR) cannot be dissolved in water, they will need to be split or weighed for tapering, or converted into equivalent immediate-release tablets for tapering with tablet combinations or liquid (see above).

http://www.drugs.com/uk/anafranil-75mg-sr-tablets-spc-11864.html
 

Quote

What Anafranil contains
Each film coated tablet contains 75mg clomipramine hydrochloride in a sustained release formulation. The tablets are formulated to release the active ingredient slowly. The tablet contains the following inactive ingredients colloidal anhydrous silica, calcium hydrogen phosphate, calcium stearate, hypromellose, red iron oxide (E172), Ethylacrylate methylmethacrylate copolymer, hypromellose, polyethoxylated castor oils, Talc and Titanium dioxide (E171).

What Anafranil looks like and contents of the pack
Anafranil 75 mg sustained release Tablets are pink capsule shaped film coated tablets marked S breakline T on both sides of the tablet.
 
The tablets come in calendar blister packs containing 28 tablets.

Who makes and repackages your medicine?
This product is manufactured by Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina km 30,400 [/size]– [/size]00040 Pomezia, Rome, Italy. and is procured from within the EU and repackaged by the Product Licence holder: Primecrown Ltd, 4/5 Northolt Trading Estate, Belvue Road, Northolt, Middlesex, UB5 5QS.

 

Use a digital scale to weigh tablet fragments or powder

For small amounts of the drug, weighing tablet fragments or powder from the If you wish to weigh the powder, see Using a digital scale to measure doses

 

You will probably find using a liquid to be much more convenient when tapering by amounts smaller than 10mg.

Edited June 22, 2022 by Altostrata
updated

[Estman]

On 12/29/2018 at 9:23 PM, Altostrata said:

Clomipramine is an older tricyclic antidepressant like amitriptyline and nortriptyline. It is a chemical derivative or analog of another TCA, imipramine. Of the TCAs, imipramine and clomipramine are the most potent serotonin reuptake inhibitors.

 

About clomipramine, from official US FDA information at dailymed.nlm.nih.gov:

 

 

Clomipramine is metabolized via liver enzymes P450 CYP2D6 and 3A4 (it is a CYP1A2 inhibitor) ; it may conflict with other drugs utilizing those liver enzymes.

 

With its active metabolite, desmethylclomipramine (DMI) or norclomipramine, clomipramine has a long half-life of about 54-77 hours.

 

From US FDA information at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b1739aa5-69d8-4a69-be58-6d789ea2a516

 

Brand-name Anafranil and generic clomipramine are supplied in 25 mg, 50 mg, 75 mg capsules. Generics may also be available in 10mg, 25mg, 50mg tablets. Clomipramine is freely soluble in water.

 

Reduce by 10% per month to start

The 10% rule holds for clomipramine, just like other psychiatric drugs: Reduce by 10% per month, calculated on the last dosage. (The amount of the reduction gets progressively smaller.)

 

See Why taper by 10% of my dosage?

 

Use a combination of clomipramine dosages to taper

If you are taking, for example, 150mg, you may wish to get 50mg of your prescription in 10mg tablets (if available). This will enable you to decrease by 10mg at a time.

 

(To justify a prescription comprised of various dosage capsules or tablets for insurance coverage, your doctor may need to indicate split dosing -- taking the drug more than once a day.)

 

When you are down to 100mg, you may wish to have your prescription filled with 50mg capsules or tablets plus 10mg tablets and carefully split the tablets until you are down to 50mg.

 

The smallest decrease you can make with available tablet sizes would be 2.5mg -- 1/4 of a 10mg tablet. Accurately cutting a tablet into quarters can be difficult. When you need to make a decrease smaller than 5mg (half a 10mg tablet), you may wish to to cut up tablets, weigh the powder (from the capsules), get a prescription for the liquid, or make a liquid to continue a 10% taper.

 

At 50mg and lower, you may wish to combine whole 25mg capsules or tablets with partial tablets or powder from the capsule weighed for accuracy, or a liquid to fill out the rest of your daily dose.

 

Use a digital scale to weigh tablet fragments or powder

For small amounts of the drug, weighing tablet fragments or powder from the If you wish to weigh the powder, see Using a digital scale to measure doses

 

You will probably find using a liquid to be much more convenient when tapering by amounts smaller than 10mg.

 

Make a clomipramine liquid yourself from tablets or capsules

Clomipramine is soluble in water. See How to make a liquid from tablets or capsules

 

Use an oral syringe to precisely measure out doses as small as .01mg.

 

Have a compounding pharmacy make custom capsules or a liquid
Compounding pharmacies can make capsules with custom dosages or a liquid from the powder. You will need a prescription written for any  compounding. The only drawback is insurance may not cover it; it can be quite expensive.

Clomipramine is a very strong SRI.[64][65] Its affinity for the SERT was reported in one study using human tissues to be 0.14 nM, which is considerably higher than that of other TCAs.[35][57] For example, the TCAs with the next highest affinities for the SERT in the study were imipramine, amitriptyline, and dosulepin (dothiepin), with Ki values of 1.4 nM, 4.3 nM, and 8.3 nM, respectively.[57] In addition, clomipramine has a terminal half-life that is around twice as long as that of amitriptyline and imipramine.[57][66] In spite of these differences however, clomipramine is used clinically at the same usual dosages as other serotonergic TCAs (100–200 mg/day).[57] It achieves typical circulating concentrations that are similar in range to those of other TCAs but with an upper limit that is around twice that of amitriptyline and imipramine.[57] For these reasons, clomipramine is the most potent SRI among the TCAs and is far stronger as an SRI than other TCAs at typical clinical dosages.[64][65] In addition, clomipramine is more potent as an SRI than any selective serotonin reuptake inhibitors (SSRIs), it is more potent than paroxetine, which is the strongest SSRI.[57]

A positron emission tomography study found that a single low dose of 10 mg clomipramine to healthy volunteers resulted in 81.1% occupancy of the SERT, which was comparable to the 84.9% SERT occupancy by 50 mg fluvoxamine.[51] In the study, single doses of 5 to 50 mg clomipramine resulted in 67.2 to 94.0% SERT occupancy while single doses of 12.5 to 50 mg fluvoxamine resulted in 28.4 to 84.9% SERT occupancy.[51] Chronic treatment with higher doses was able to achieve up to 100.0% SERT occupancy with clomipramine and up to 93.6% SERT occupancy with fluvoxamine.[51] Other studies have found 83% SERT occupancy with 20 mg/day paroxetine and 77% SERT occupancy with 20 mg/day citalopram.[51][67] These results indicate that very low doses of clomipramine are able to substantially occupy the SERT and that clomipramine achieves higher occupancy of the SERT than SSRIs at comparable doses.[51][62] Moreover, clomipramine may be able to achieve more complete occupancy of the SERT at high doses, at least relative to fluvoxamine.[51]

If the ratios of the 80% SERT occupancy dosage and the approved clinical dosage range are calculated and compared for SSRIs, SNRIs, and clomipramine, it can be deduced that clomipramine is by far the strongest SRI used medically.[62][61] The lowest approved dosage of clomipramine can be estimated to be roughly comparable in SERT occupancy to the maximum approved dosages of the strongest SSRIs and SNRIs.[62][61] Because their mechanism of action was originally not known and dose-ranging studies were never conducted, first-generation antipsychotics were dramatically overdosed in patients.[62] It has been suggested that the same may have been true for clomipramine and other TCAs.[62]

 

Does clomipramine 10mg seem to be as strong as 20mg paroxetine?
Does this mean that withdrawal symptoms are also the most severe?

[dangerous7]

I have 10mg Clomipramine tablet and want to reinstate 0.5mg. Is it ok to crush the powder and measure 1/20th of that in a digital scale to obtain 0.5mg?

[ChessieCat]

8 hours ago, dangerous7 said:

I have 10mg Clomipramine tablet and want to reinstate 0.5mg. Is it ok to crush the powder and measure 1/20th of that in a digital scale to obtain 0.5mg?

 

From Post #1:

 

On 12/30/2018 at 6:23 AM, Altostrata said:

Use a digital scale to weigh tablet fragments or powder

For small amounts of the drug, weighing tablet fragments or powder from the If you wish to weigh the powder, see Using a digital scale to measure doses

 

You will probably find using a liquid to be much more convenient when tapering by amounts smaller than 10mg.

 

[ChessieCat]

On 3/17/2021 at 12:41 AM, Estman said:

Does clomipramine 10mg seem to be as strong as 20mg paroxetine?
Does this mean that withdrawal symptoms are also the most severe?

 

Have you seen this topic?  why-taper-sert-transporter-occupancy-studies-show-importance-of-gradual-change-in-plasma-concentration

 

Withdrawal symptoms are related to how much drug has been taken away.  Generally the more drug taken away in one go, the worse the withdrawal symptoms are because the brain has tomore adaptions because it is getting less of the drug.  That is why it is better to listen to your body/symptoms and not to make another reduction unless you are stable.

 

The idea with tapering is that the drug is taken away a small amount at a time which means that the brain doesn't need to make as many changes.  It adapts as you taper.  It doesn't necessarily mean you will have a symptom free taper, but hopefully it will keep withdrawal symptoms to a minimum, because you are "sneaking the drug away" little by little.

 

Using information from this post dose-equivalents-equivalency-comparison-for-antidepressants-and-second-generation-antipsychotics

 

paroxetine dosage of 34.0mg/day,

 

clomipramine 116.1mg/day,

 

 

Therefore

 

20mg paroxetine = ~ 68mg clomipramine.

 

OR

 

10mg clomipramine = ~3mg paroxetine

 

BUT it is important to understand that different drugs "work" different ways. 

[Maggs]

This is fantastic information Altostrata. I'm very grateful. Hopefully I will be able to reduce from Clomiprimine without too many problems.

Thank you