Treating OCD with Minocyline

[LNN]

http://www.washingtonpost.com/sf/national/2016/03/21/beyond-the-catchphrase/

 

This article talks about using minocyline to regulate glutamate receptors - some patients saw their OCD melt away.

[T_Mom]

THANK YOU for posting this LLM!!! Great article...and makes me want to run there tomorrow to see what they think.

wow!

[LNN]

T_Mom!! How are you?!!

[T_Mom]

llm--Our eldest, is great, headed to college next year, and academically strong. (We are so thankful.) I think it was having pheresis followed by IVIG a few months later.) She has been clear for 3 years, and weaned herself off of abx. (she told me last week.)

 

For the younger, struggling continues. Less volatility, but OCD is crippling, and academic failure. Able to only do 4 of 8 classes this year and last. Still struggling.

 

IVIG 8 weeks ago, saw good improvement, and then she started declining at 4 weeks post-IVIG, tried IV steroids at 6 weeks post-IVIG, helped a bit, and now two weeks later continuing to decline. Hard times.

[LNN]

Yay for your oldest!!! Like yours, mine is off meds (3 yrs now) and an academic success. The kid who we once argued about holding back is an honors student and headed into HS next year, complete with obnoxious teen attitude. I used to tell people that because they're supposed to outgrow pandas, I was the only mom I knew who looked forward to having a teen. I should've known better! But at least it's normal stuff and I'm happy to turn gray over simple things.

 

Like you, my youngest is struggling. Thankfully OCD is minimal but she's often a stunt-double for Linda Blair in the Exorcist. She's just about mastered the head spinning completely around and instead of hurling projectile vomit, she hurls insults and irrational accusations. She battled mold issues in school last year - almost landed her in the hospital twice. So she's homeschooled this year - something we never imagined doing. The issues from last year took a toll on her and in Nov. she crashed, developing a range of neurological issues. Still trying to dig out of that hole (lab results pending for a variety of things). But...with every suckish challenge, there are gifts. Homeschooling has been an awesome experience - her self-confidence has returned, she's able to move at a pace that's good for her health, and no skeptical administrators to make us feel defensive and stressed. She's developed a full range of creative interests and is considering homeschool next year, whether her health requires it or not.

 

So I feel like I'm 80 yrs old, but at least we can both look to our first borns and know it can be done! I hope your journey starts to get easier - you so deserve it!

[MomWithOCDSon]

Not to hijack the thread (thanks for a great article, LLM!) . . .

 

TMom and LLM, congrats on your success with your oldest kids! Hopefully, reveling and basking in that glow will give you the additional strength and resilience you need to get your younger kids where they need to be. From our personal experience, I do think there's something to the sense that they can "grow out of it," at least to some extent.

 

All the best!

[LNN]

Thanks, Nancy. I did mention he's headed into HS, right? Which makes him 13 right now. So no reveling or basking. The only glow is the irritation coming off my red cheeks as we argue over why it's not appropriate to take your black dress clothes for today's dress rehearsal (production crew for the school play) and wad them up into your backback. Apparently, I am incredibly out of line for suggesting one should not look like they've slept in their clothes or dug them up from the bottom of the hamper when one is part of a school play.

 

But as successful as your DS is, surely you've been down this path. I'll assume your image of my basking is painted in jest! But yes, we will get kid #2 better. And then someday I'll have Grandkids and that will be the sweetest revenge nature bestows!

[T_Mom]

Good to hear the positive update LLM !! and to see you are doing well MomWithOCDSon ! Yes, having an older teen -- senior in HS and heading to college makes me hopeful. I am sorry your youngest is still wrestling with issues though LLM, and I understand the age related fatigue!!! Home schooling in middle and high school is more than admirable -- good for you !!!! Thanks again for sharing the article-- our youngest was switched to it today.

Edited March 24, 2016 by t_mom

[chubbermommy]

Does anyone know what dosing of minocycline was used in this study? I can't seem to find?

[jan251]

I just want to tack on a really interesting study I came across about minocycline.

 

Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice.

 

male offspring during adolescence (PND 21-40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early life inflammation in adulthood.

 

What is so interesting to me is not so much that neonatal inflammation had long-lasting effects (this fits with my general perspective and personal experience with my ds, who had his share of issues as a neonate) but especially that the minocycline during adolescence improved the problem.

 

(Unfortunately, we tried mino a few times before and ended up stopping after a short time due to increased sound sensitivity, which is already a major issue for my ds. At this point, I'm suspecting that may be a herx, and while I'm not big on pushing through negative symptoms, I wonder how long we could manage to get through, maybe with the addition of NAC.)

[Ladymavs]

My son has always responded to azith in past flare ups with the OCD/intrusive thoughts since PANS onset back in fall of 2013. However, when he flared up again this past spring, we tried the azith again and he did not seem to respond. Eventually, the OCD got so bad that we took a trip to the ER. There, he was put on low dose risperdal (.25mg twice daily) which we are starting to wean. We recently added zoloft and are currently at 25mg. We just moved up from 12.5mg and it does seem to increase the OCD initially which I read is common...so hopefully it will settle in the next week or two or we will be going something different. Our issue has always been primarily high MYCO P and we just tested his levels again and hope to have results early next week. Our PANDAS doc has mentioned doxy in past visits since we have been through the azith, biaxin, and omnicef. In reading, it sounds like mino may be a better choice as it crosses the BB. We are currently doing CBT and will be getting into the ERP part in the next couple of weeks...so I want to do all we can to continue trying to bring down the OCD to make therapy effective. Anyone have experience with zoloft? Mino?

[MomWithOCDSon]

No experience with mino, but very interested to hear from folks who try it.

 

But Zoloft, yes. My DS took has taken it for a few years now; we started it during his penultimate PANDAS episode based on some research and information I gleaned from a session at the IOCDF conference that year and, in particular, a panel led by Dr. Eric Storch. It just seemed like it might be a good fit for our DS, and it has been. That said, I think you're wise to take it "low and slow," just because there are so many moving parts to how people respond to these medications.

 

All the best!

[Ladymavs]

Our PANS doctor wanted us to go back to azith and give it some time to work as this seems to be the first line of defense in battling myco p. He also wrote script for mino in the event that the azith did not bring improvement in 2-3 weeks. However, I keep reading many on a PANS forum that you need an abx combo to really combat myco p. Many have used azith + augmentin or another combination. Is this the case--could it be that we need to ask for another abx to help the azith? The PDOC said to stay at the zoloft 25mg and see if the abx brings relief. If they show no improvement, he said we could go to 50mg zoloft and see if that helps with the OCD/intrusive thoughts. The thoughts are so tiresome and I know my son is ready to get some real relief. We are doing CBT and about to get into the ERP portion of therapy within a couple of weeks. I really hope this brings a breakthrough as we need it.

[jan251]

Another study on minocycline and OCD:

 

Minocycline combination therapy with fluvoxamine in moderate to severe obsessive-compulsive disorder: A placebo-controlled, double-blind, randomized trial.

METHODS: One hundred and two patients with the diagnosis of moderate to severe OCD were recruited to this study. A randomized double-blind trial was designed and patients received either L-carnosine or placebo as adjuvant to fluvoxamine for ten weeks. The patients randomly received either minocycline 100 mg twice per day or placebo for ten weeks. All patients received fluvoxamine (100mg/day) for first 4 weeks, followed by 200 mg/day for the rest of the trial, regardless of their treatment groups.

CONCLUSION: A significantly greater rate of partial and complete response was observed in the minocycline group (p <0.001). The frequency of side effects was not significantly different between the treatment arms

I wonder what happens after the mino is withdrawn?

More mino studies:

Minocycline attenuates interferon-α-induced impairments in rat fear extinction.

RESULTS: Infusing the amygdala with IFN-α impaired the extinction of conditioned fear in rats and activated microglia and astrocytes in the amygdala. Administering minocycline prevented IFN-α from impairing fear extinction. The immunohistochemical and biochemical results show that minocycline inhibited IFN-α-induced microglial activation and reduced IL-1β and TNF-α production.

CONCLUSIONS: Our findings suggest that IFN-α disrupts the extinction of auditory fear by activating glia in the amygdala and provides direction for clinical studies of novel treatments to modulate the innate immune system in patients with psychotic disorders.

Autism phenotypes in ZnT3 null mice: Involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation.

Consistent with known roles for MMPs in BDNF upregulation, 2.5-week treatment with minocycline, an MMP inhibitor, significantly attenuated BDNF levels as well as megalencephaly and autistic-like behaviors.

On the other hand:

Microglia Activation and Schizophrenia: Lessons From the Effects of Minocycline on Postnatal Neurogenesis, Neuronal Survival and Synaptic Pruning.

However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively. These deleterious effects contrast with the neuroprotective actions of minocycline at adult stages. They are of potential importance for schizophrenia, since minocycline triggers similar pro-apoptotic effects in the developing brain as NMDA receptor (NMDAR) antagonists, known to induce long-term schizophrenia-like abnormalities. Moreover, altered postnatal neurogenesis, recently described in the human striatum, was proposed to induce striatal dopamine dysregulation associated with schizophrenia. Finally, the effect of minocycline on synapse remodeling is of interest considering the recently reported strong genetic association of the pruning-regulating complement factor gene C4A with schizophrenia. This raises the exciting possibility that in conditions of hyperactive synaptic pruning, as supposed in schizophrenia, the inhibitory action of minocycline turns into a beneficial effect, with relevance for early therapeutic interventions. Altogether, these data support a differential view on microglia activation and its inhibition.

And orthodontics can induce glial activation? who knew?

Effect of minocycline on induced glial activation by experimental tooth movement.

RESULTS: There was a significant increase in the OX42 and glial fibrillary acidic protein immunoreactivity in response to tooth movement in the medullary dorsal horn. Furthermore, systematic administration of minocycline, a selective inhibitor of microglial activation, significantly attenuated the nociceptive c-Fos expression in the medullary dorsal horn that was induced by experimental tooth movement.

CONCLUSIONS: These data indicate the possible importance of microglial activation in the development of orthodontic pain. This is also the first report on the systematic application of minocycline.

 

(Interestingly, it appears Dr. Swedo also did a study: A pilot open-label trial of minocycline in patients with autism and regressive features, where there were changes in CSF but not in symptoms)

 

There is a minocycline study underway, Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD, though no results have been posted. This trial requires current SSRIs with minimal but insufficient improvement. PANDAS patients are excluded.

Edited September 25, 2016 by jan251

[Ladymavs]

We are almost 30 days into minocycline for mycoplasma and has had no dent in the OCD thus far. We had tried zoloft during the summer and were up to 25mg for several weeks and noticed nothing, so we opted not to increase. My thought that we should see some difference if it were working and would have moved up had that been the case. I would like to get these underlying issues addressed with mycoplasma and hhv6, but may have to consider another SSRI to help dampen the OCD thoughts if at all possible.