Taper off Effexor XR or keep trying add-ons?

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Glad I found this site. I am 37 and suffer from Major Depressive Disorder (Recurrent), GAD, Panic Disorder and OCD. I was on Paxil for 10 years when it pooped out and now I've been on Effexor XR 225mg for the last 12 years and started having issues in February to the point of panic attacks. They upped my Effexor to 300mg. I have also been on Buspar for two years. They doubled that to 60mg daily. They gave me Ativan to help with the panic and started me on Abilify as an add-on. The Abilify made me too restless, so now they're trying me on Rexulti, but I'm not sure if it will work. My only other options are try other add-ons (Seroquel, Remeron, etc) or start tapering slowly the Effexor for an antidepressant overhaul. I don't feel I'm where I need to be in terms of my anxiety being too much and I feel like a zombie and tired but I'm not sure which med(s) are causing it. Any advice on the best route? I know Effexor can be a bear to come off of but I'd do it very slowly per my Dr and PA. Is it worth fiddling with other add-ons?

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  • Posted

    Wow. 300 mg of Effexor (venlafaxine) is a huge dose. I mean it – normally patients do not get even close to this number. Whether staying on it for a prolonged period of time is a wise thing to do… Probably not. At 300 mg it loses its selectivity and inhibits the re-uptake of all three major neurotransmitters – serotonin, noradrenaline and dopamine. I see no point in adding an antipsychotic medication – venlafaxine at this dose already affects your dopamine levels and all Abilify can do is to increase the number of side effects that you experience (in the case of this combo at the dose you mentioned you must feel like a total zombie, and probably this is the main cause of your anxiety). On the other hand – you cannot just quit venlafaxine cold turkey from 300 mg – tapering is probably going to take at least half a year.

    Here is what I can suggest – but mind that I am not a psychiatrist and you really need a second opinion on this. You could gradually withdraw venlafaxine by reducing the dose by no more than 37.5 mg per 2 weeks. In the same time, you could ask your pdoc for diazepam script – start with 5 mg tablets. Once you reduce the venlafaxine dose and the anxiety starts increasing, you would need to start taking diazepam and eventually increase the dose to 10 – 30 mg per day (again – this is a huge dose that would certainly result in the development of tolerance and benzodiazepine addiction – this is why it is important that you get diazepam and not any other benzodiazepine (like Ativan) - diazepam dependence is relatively ‘easy’ to overcome).

    Once venlafaxine is no longer present in your system, I would start a treatment with MAO inhibitors – either the more sedating phenelzine (Nardil) or the more activating pranylcypromine (Parnate). These drugs belong to an older generation of antidepressants and also increase the levels of all three neurotransmitters. However, they do it in a totally different way that does not turn people into zombies. There would be two drawbacks to this solution: (1) You would need to follow a strict diet with products like cheese, cured meat, beer or yeast extracts being banned forever, and (2) you would eventually need to withdraw diazepam, which is likely to be a painful experience. The total time until the switch is complete could be anywhere between 6 months and a year. But it could be worth it – the majority of patients with underlying anxiety issues who don’t respond to SSRI/SNRI, respond very well to MAO inhibitors.

    • Posted

      Does clobazam for epilepsy affect the dopamine levls as well ? thanks
    • Posted

      Hi Jane,

      No, being a benzodiazepine, clobazam binds to the GABA receptor group and controls the polarisation of neurons. This mechanism of action is entirely different to the re-uptake inhibition of neurotransmitters (like in SSRI/SNRI) or preventing their breakdown (like in the case of MAOi).

    • Posted

      Thanks. So clobazam does not cause any problems I take it.
    • Posted

      Having tried ssri s and trycyclics with no abatement of depression and anxiety, i am left on a low dose diazepam and its not dealing with the problem.  I dont want to increase it for obvious reasons.  My psych is new and has suggested augmenting with atypical antipsychotic.  I do not have psychosis. Do you think MAO would be better way to go, i am on lifetime warfarin but know about the food issues.  I wonder if many people take these nowadays but would try anything to help.
    • Posted

      Hi Ann,

      Interactions between warfarin and MAOi have been poorly investigated. I am aware of only one paper reporting that tranylcypromine and warfarin administered in combination caused problems as both of these medications are metabolised by the p450 system (CYP2C19 to be specific). Mind that this is not the kind of interaction that can lead to a hypertensive crisis, but as the metabolism rate of both substances becomes impossible to predict, a pdoc would probably consider starting such therapy only on an in-patient ward (at least during the initial few weeks), where the concentration of both drugs in your system could be quickly determined (if a dangerous interaction occurred).

      Regarding the other MAOi that you could consider (phenelzine, selegiline) - I cannot tell. There are no data. It really depends on whether you would be willing to try and whether your pdoc would consider taking the risk / putting his career on the line...

       

    • Posted

      I doubt he would, thats why hes in favour of using atypical antipsychotics as he is obviously used to using them.   I am not so sure I want to take that risk so am looking for alternatives.
    • Posted

      Ann, it sounds like you have no alternatives. Normally I would suggest trying MAOi but in your case the risk is just too high. Surely having a fully functional cardiovascular system is more important than ‘feeling good’ (well – at least this is what any clinician would say…).

      If you decided to go ahead with the antipsychotics route, do your research first. While all modern antipsychotics are equally effective, their side effect profiles are different. Olanzapine is highly sedating and induces some serious weight gain, so I would certainly say no to this one. By weight gain I mean putting up 20 - 30 kg in a few months’ time. It is also known to dramatically increase prolactin levels in women, which can cause further problems. Risperidone is rather activating. While this feature makes it very useful for people suffering from negative symptoms of schizophrenia (or from bipolar depression), it can increase anxiety. Aripiprazole (trade name Abilify) could be a good compromise. It composes well with sertraline – this is probably the most common SSRI + antipsychotic combination, which means that pdocs usually have experience in managing the augmented therapy. You could start with 5 mg of aripiprazole and 100 mg sertraline and eventually increase the antipsychotic dose to 10 mg. Side effects… weight gain (though not as severe as with olanzapine) and very slow development of tardive dyskinesia. Probably you would not notice any involuntary movements after taking aripiprazole for a year, but staying on it for many years would require a careful risk vs benefits evaluation.

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