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Dose Equivalents for Antidepressants and Second-Generation Antipsychotics

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DoctorMussyWasHere

A potentially useful resource: Dose Equivalents for Second-Generation Antipsychotics: The Minimum Effective Dose Method

The article includes a huge table of equivalent doses and studies. Here's the dose data extracted:

 

Amisulpride 100 400 800 1200            
Aripiprazole 2 5 10 15 20 30        
Asenapine 0.4 0.8 1.6 3.2 4.8 10 20      
Clozapinec 100 300 600              
Haloperidol 4 4.5 6 8 10 12 15 15±5 16 20
Iloperidone 4 4–8 8 10–16 12 12–16 20–24 24    
Lurasidone 20 40 80 120 160          
Olanzapine 1 5±2.5 10 10±2.5 15 15±2.55        
Paliperidone 1.5 3 6 9 12 15        
Quetiapine 75 150 <250 250 300 400 450 600 750 800
Risperidone 2 4 6 8 10 12 16      
Sertindole 8 12 16 20 24          
Ziprasidone 10 40 80 120 160 200        
Zotepine 75 150 300              

 

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Altostrata
Posted (edited)

J Affect Disord. 2015 Jul 15;180:179-84. doi: 10.1016/j.jad.2015.03.021. Epub 2015 Mar 31.

Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.

Hayasaka Y1, Purgato M2, Magni LR3, Ogawa Y1, Takeshima N1, Cipriani A4, Barbui C2, Leucht S5, Furukawa TA1.

 

Abstract at https://www.ncbi.nlm.nih.gov/pubmed/25911132 Free full text at https://www.sciencedirect.com/science/article/pii/S0165032715001512

 

BACKGROUND:

Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method.

 

METHODS:

We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d.

 

RESULTS:

We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin.

 

LIMITATIONS:

The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants.

 

CONCLUSIONS:

Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.

Edited by Altostrata
updated link

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Altostrata
Posted (edited)

ADMIN NOTE: Many clinicians believe dosage may be reduced when acute phase (dramatic symptoms) is over. We recommend a very, very gradual reduction to avoid destabilization that might send you back to the acute phase dosage.


 

Schizophr Res. 2018 Mar;193:23-28. doi: 10.1016/j.schres.2017.07.033. Epub 2017 Jul 21.

Dose equivalents for second generation long-acting injectable antipsychotics: The minimum effective dose method.

Rothe PH1, Heres S2, Leucht S2.

 

Abstract at https://www.ncbi.nlm.nih.gov/pubmed/28735640

 

BACKGROUND:

The concept of dose equivalence of depot medication is important for many scientific and clinical purposes.

 

METHODS:

A systematic literature search on four second-generation antipsychotics available as long-acting injectable drugs and haloperidol was conducted. We used the minimum effective dose method which is based on randomized fixed dose studies where the smallest dose which was significantly more efficacious than placebo in the primary outcome was declared as minimum effective dose. We calculated equivalent doses from acute phase studies but we also reported the minimum effective doses found in relapse prevention studies.

 

RESULTS:

The acute phase minimum effective doses/olanzapine equivalents were: aripiprazole lauroxil 441mg (300mg aripiprazole)/4wks/0.71; aripiprazole 400mg/4weeks/0.95 (aripiprazole maintena); paliperidone palmitate 25mg/4weeks/0,06; risperidone 25mg/2weeks/0,12; RBP-7000 90mg/4weeks/0,21; olanzapine 210mg/2weeks/1.

 

CONCLUSIONS:

The minimum effective dose method is an operationalized and evidence-based approach for determining antipsychotic dose equivalence which can also be applied to long-acting injectable formulations. Doses may not have been chosen low enough to find the truly minimum effective dose. Comparisons with other methods will be necessary to come to ultimate conclusions.

Edited by Altostrata
updated

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Altostrata

ADMIN NOTE This is useful because it gives dosage ranges for these drugs.


 

https://psychopharmacologyinstitute.com/antipsychotics/long-acting-injectable-antipsychotics-a-practical-guide-for-prescribers/

 

Long-Acting Injectable Antipsychotics: A Practical Guide for Prescribers

 

Author: Flavio Guzman, MD
Last updated: February 10, 2018
Competing interests: none

 

This article summarizes the most clinically relevant features of long-acting injectable antipsychotics (LAIs, previously known as depot antipsychotics). We discuss general concepts as well as key prescribing facts of individual agents.


The guide also includes two new formulations: aripiprazole lauroxil (Aristada) and 3-month paliperidone palmitate (Invega Trinza).

Advantages and disadvantages of long-acting antipsychotics

Brissos and colleagues [1] reviewed the role of long-acting injectables in schizophrenia. They summarized the key advantages and disadvantages of LAIs in clinical practice.

Potential advantages

  • Early identification of non-adherence
  • Providing a mechanism for monitoring adherence with injections
  • No need to remember to take medication every day
  • Regular interactions between patient and medical staff
  • Reduced relapse frequency and rehospitalization rates
  • Clear attribution of the cause of relapse or non-response, discriminating between non adherence or lack
    of response
  • Reduce the risk of accidental or deliberated overdose
  • Treating patients with more stable plasma concentrations than oral medications
  • Avoidance of first-pass metabolism – better relationship between dose and blood level of drug
  • Lower and less frequent peak plasma level – reduced side effects

Potential disadvantages

  • Slow dose titration
  • Longer time to achieve steady state levels
  • Less flexibility of dose adjustment
  • Delayed disappearance of distressing and/or severe side effects
  • Pain at the injection site can occur, and leakage into the subcutaneous tissue and/or the skin may cause irritation and lesions (especially for oily long-acting injectable)
  • Burden of frequent travel to outpatient clinics or home visits by community nurses for their administration
  • Risperidone long-acting injectable needs refrigeration, which may be cumbersome in some latitudes
  • Perception of stigma

Clinical questions answered

Castillo and Stroup [2] reviewed the effectiveness of LAIs and addressed the following questions:

Who should receive LAIs?

Consider LAIs for patients with recent-onset schizophrenia and those with risk factors for medication non-adherence: history of non-adherence, severe symptoms, comorbid substance use, cognitive impairment, ambivalence or negative attitudes towards medications, and poor insight.

Are the newer LAIs more effective?

The effectiveness of newer LAIs (aripiprazole, olanzapine, paliperidone and risperidone) and older LAIs (haloperidol,fluphenazine, flupenthixol) is similar.

Tables summarizing individual agents

First-generation antipsychotics available as long-acting injectable medications

 

Drug Starting dose (mg) Maintenance dose (mg)
Haloperidol decanoate 50 50–200 every 3–4 weeks
Fluphenazine decanoate 12.5 12.5 – 50 every 2–3 weeks
Flupenthixol decanoate 20 50–300 every 2–4 weeks
Zuclopenthixol decanoate 100 200–500 every 1–4 weeks

Second-generation antipsychotics available as long-acting injectable medications

Drug (Brand name) Manufacturer Available formulations Injection interval Comments
Aripiprazole monohydrate
(Abilify Mantenna)
Otsuka/ Lundbeck 300,400 mg vials, prefilled syringes 400 mg once/month Requires a period of 2 weeks of overlap with oral aripiprazole.
Aripiprazole lauroxil
(Aristada)
Alkermes 441, 662, 882 mg prefilled syringes 441–882 mg once/month
882 mg q 6 weeks
The 882 mg dose can be administered every 6 weeks.
Requires a period of 3 weeks of overlap with oral aripiprazole.
Olanzapine pamoate
(Zyprexa Relprevv)
Lilly 210, 300, 405 mg vials 150–300 mg q2 weeks
300–405 mg once/month
Requires monitoring post injection (3 hours)

Paliperidone palmitate
(Invega Sustenna, Xeplion)

 

Janssen 39,78,117,156 or 234 mg prefilled syringes 117 mg once/month Oral supplementation not necessary.
Paliperidone palmitate
(Invega Trinza)
Janssen 273, 410, 546, 819 mg prefilled syringes 410 mg q3 months Use in patients already treated with Invega Sustenna
Risperidone microspheres

 

(Risperdal Consta)

 

 

 

Janssen

 

 

 

12.5, 25, 37.5 or 50 mg vials

 

 

 

25 mg q2 weeks

 

 

Requires a period of 3 weeks of overlap with oral risperidone

Practical considerations

Abilify Mantenna

  • Aripiprazole monohydrate requires a period of overlap of 2 weeks with oral aripiprazole.
  • Available as a lyophilized powder which needs to be reconstituted.

See full prescribing information (PDF)

Aristada

  • Aripiprazole lauroxil requires a period of overlap of 3 weeks with oral aripiprazole.
  • Available as a prefilled syringe that does not require reconstitution.

See full prescribing information (PDF)

Highlights of prescribing information

Zyprexa Relprevv

  • Olanzapine pamoate does not need overlap with oral olanzapine.
  • It has a small risk of post-injection syndrome (0.07% of injections):
    • Symptoms include sedation, confusion, agitation, anxiety, aggressiveness, dizziness, ataxia and extrapyramidal symptoms
    • This risk limits use olanzapine pamoate use
    • After injection, the patient must be monitored for three hours by a healthcare professional
    • In the US, prescribers who administer Zyprexa Relprevv must enroll in a national registry that documents the incidence of this adverse effect

See full prescribing information (PDF)

Invega Sustenna

  • Paliperidone palmitate does not need overlap with oral paliperidone.
  • Requires two separate loading dose injections during the first week.

See full prescribing information (PDF)

Invega Trinza

  • The 3-month paliperidone palmitate (PPM–3) formulation can only be used if the patient has been receiving 1-month paliperidone palmitate injections for at least 4 months.
  • It is administered 4 times a year, providing the longest interval of any approved LAI.

See full prescribing information (PDF)

Risperdal Consta

  • Risperidone microspheres requires a period of overlap of 3 weeks with oral risperidone.
  • It has a 2-week dosing interval.

See full prescribing information (PDF)

Acknowledgements: Thanks to Dr. Leslie Lundt for correcting an earlier version of this article.

References

  1. Brissos, S., Veguilla, M. R., Taylor, D., & Balanzá-Martinez, V. (2014). The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal. Therapeutic advances in psychopharmacology, 2045125314540297. 
  2. Castillo, E. G., & Stroup, T. S. (2015). Effectiveness of long-acting injectable antipsychotics: a clinical perspective. Evidence Based Mental Health, ebmental–2015. 
  3. Gopalakrishna, G., Aggarwal, A., & Lauriello, J. (2013). Long-acting injectable aripiprazole: how might it fit in our tool box?. Clinical schizophrenia & related psychoses7(2), 87-92.
  4. Citrome, L. (2015). Aripiprazole long-acting injectable formulations for schizophrenia: aripiprazole monohydrate and aripiprazole lauroxil.Expert review of clinical pharmacology, 1-18.

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bubbles
On 5/9/2018 at 5:35 AM, Altostrata said:

J Affect Disord. 2015 Jul 15;180:179-84. doi: 10.1016/j.jad.2015.03.021. Epub 2015 Mar 31.

Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials.

Hayasaka Y1, Purgato M2, Magni LR3, Ogawa Y1, Takeshima N1, Cipriani A4, Barbui C2, Leucht S5, Furukawa TA1.

 

I wonder if the link to this article further up in the thread is broken. I found it here: https://www.sciencedirect.com/science/article/pii/S0165032715001512

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Altostrata

The link works fine for me, bubbles. I have added your link to the post as well.

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bubbles

Thanks Alto. The first "full text" link in that post is taking me to the antipsychotic article, not the antidepressant article.

Cheers!

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Altostrata

Thanks, bubbles, correction made.

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