Is Paliperidone Palmitate depot a better one for Schizophrenia?:Schiz Bulletin: Nov:2012

28.11.2012

About 80% of patients with Schizophrenia  recover from their first episode of illness. Of these, approximately 80% then go on to relapse within 5 years (Robinson 1999). 5–10% of people with schizophrenia are thought to complete suicide(Palmer 2005). Treatment adherence is a crucial factor in preventing relapse.Up to 60% patients might be partially or totally non adherent to treatment. Long acting antipsychotic injections  (depot injections) were developed in 1960s with the aim of improving adherence. First generation depot injections were developed in 1960s. The first Second Generation LAI to get regulatory approval was Risperidone LAI in 2003. Currently BNF ( Nov 2012) lists 8 depot antipsychotics of which  5 are FGAs (Flupenthixol deconoate, Fluphenazine decanoate, Haloperidol, , Pipotiazine Palmitate, Zuclopenthixol decanoate) and 3 SGAs ( Risperidone LAI, Olanzapine embonate, Paliperidone Palmitate). Paliperidone Palmitate was approved by FDA in 2009 and is available in Europe since 2011.

Is Paliperidone Palmitate a better depot ?

Nussbaum and Stroup did a metanalyisis to compare effects of Paliperidone Palmitate with any other treatment for people with schizophrenia and schizophrenia-like illnesses.The search strategy was comprehensive (Cochrane methodology)

Authors identified seven  RCTs that met all inclusion criteria.

1. Kramer 2009:  duration of study 64 days: N= 247:Against Placebo.

2. Hough 2010:  flexible duration. randomised stage : 171 days:N=410:Against Placebo.

3. Gopal 2010:  duration 13 weeks:  N=388:Against Placebo.

4. Nasrallah 2010:duration 13 weeks: N= 518:Against Placebo.

5. Pandina 2010: duration 13 weeks:N= 652:Against Placebo.

6.Fleischhacker 2010: 53 weeks (longest duration study ):N=749: Against Risperidone LAI flexibly dosed at 25, 37.5, or 50 mg.

7. Pandina 2011: duration:13 weeks:N=1220: Against Risperidone LAI  flexibly dosed at 25, 37.5, or 50 mg.

Findings

Against Placebo

1. Over two-fifths of participants left these studies before completion. Those in Paliperidone Palmitate were significantly and consistently less likely to discontinue treatment or leave early at all studied doses, except for flexible dosing.

2.Participants randomised to any dose of Paliperidone Palmitate were significantly more likely to experience a clinically important change in global state.They were also less likely to experience a recurrence of psychotic symptoms compared with placebo.

2.Consistent and significant elevation in serum prolactin that was more pronounced for women than for men seen in Paliperidone group.However,no increase in sexual side effects were found.Those in Paliperidone Palmitate group were more likely to experience an extrapyramidal movement disorder,but the effect was modest.

Against other depots

1.Two studies with 1 969 participants compared flexibly-dosed Paliperidone Palmitate with flexibly dosed Risperidone long-acting injection.Paliperiodne mean dose was 73.3 mg and 104.6 mg every 4 weeks compared with risperidone long-acting injection at mean doses, respectively, of 35.3 and 31.7mg every 2 weeks.

2.There was no difference in the the number of people leaving the study early between the two groups or on recurrence rate. The pooled data suggest less recurrence for people receiving risperidone LAI, but the finding was not statistically significant and no certain conclusions about this outcome can be made.

3. No difference in the clinical outcome when defining a clinically important change as at least a 30% reduction in PANSS scores

4. Though no difference in movement disorders,between the two groups were observed, Paliperidone group was less likely to use anticholinergic medications.

5.There was no statistically significant difference in death rate between the two group. HOWEVER, of the total of six deaths occurred in these two trials  five  occurred among people who received Paliperidone Palmitate (5  out of 986 patients)  against one death in 981 patients on Risperidone LAI. The numbers are too small to make meaningful interpretetions.

Conclusions:

Paliperidone palmitate is an effective antipsychotic whose optimal dose appears to be between 39 mg and 234 mg every four weeks in these trials. The benefits and adverse effects are similar to those of risperidone.

Comments: Paliperidone is given once monthly as against 2 weekly Risperidone LAI. This might have advantages.However, it is possible that the likely reduction in frequency of contact as a consequence, may not be beneficial in some patients.

Summary of the article:

Paliperidone palmitate for schizophrenia. Nussbaum AM, Stroup TS. Schizophr Bull. 2012 Nov;38(6):1124-7.

Full version of the Cochrane Review:

Nussbaum AM, Stroup TS. Paliperidone palmitate for schizophrenia. Cochrane Database Syst Rev. 2012s. Art. No.: CD008296. doi:10.1002/14651858.CD008296.pub2.

5 thoughts on “Is Paliperidone Palmitate depot a better one for Schizophrenia?:Schiz Bulletin: Nov:2012

  1. Period of study is too short to make any comment about disease like schizophrenia first episode., utility of injectable preparation.If EPS are common then, what is the use if patient has to take anti parkinsonian medication orally.Cause of death must had been investigated.40 % drops rate is too high.
    Dr. T.P.Jindal
    Senior Consultant Psychiatrist
    Delhi. (India)

  2. My son (33 years) died suddenly 3 days after his monthly injection of Paliperidone on 5 January 2013. I want some answers!

  3. 5.There was no statistically significant difference in death rate between the two group. HOWEVER, of the total of six deaths occurred in these two trials five occurred among people who received Paliperidone Palmitate (5 out of 986 patients) against one death in 981 patients on Risperidone LAI. The numbers are too small to make meaningful interpretetions.
    HOWEVER????? ONE DEATH IN 986 PATIENTS IS SIGNIFICANT!

    • Deaths are extremely significant events whether one or more.One cannot turn a blind eye even if it is statistically not significant.That is why those numbers were described in the summary.I am sorry to hear about your loss.Manoj

      • Paliperidone injection has not been recommended by the Scottish Medicines
        Consortium as the ‘manufacturer did not present a sufficiently robust clinical and
        economic case’. 15 Paliperidone tablets are not on the formulary of one NHS
        North East mental health trust. 13
        CAN YOU TELL ME THE MANUFACTURER’S NAME AND CONTACT DETAILS PLEASE?

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s