Minocycline For Depression: A Systematic Review And Meta-analysis Of Clinical Trials

[Logan-]

Journal of Affective Disorders
Volume 227, February 2018, Pages 219-225

Review article
Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials
Joshua D.Rosenblat Roger S.McIntyre

Highlights
•
A large antidepressant effect was observed for minocycline compared to placebo.

•
Minocycline had good tolerability with low rates of adverse effects and discontinuation.

•
Future larger RCTs of minocycline for depression are merited.

•
Future studies should also identify subgroups more likely to benefit from minocycline.

Abstract
Background
Minocycline has been identified as a potential novel treatment for depression. The objective of the current review is to determine the overall antidepressant efficacy and tolerability of minocycline.

Methods
Completed and ongoing clinical trials of minocycline for depression (both bipolar and unipolar) published prior to September 12, 2017 were identified through searching relevant databases. Using a random-effects model, data from randomized controlled trials (RCTs) were pooled to determine the antidepressant effect size of minocycline compared to placebo. Relative risk of all-cause discontinuation was determined to assess overall tolerability.

Results
Eighteen clinical studies (including published and unpublished RCTs, open label studies, ongoing clinical trials and a case report) were identified for inclusion in the qualitative synthesis. Only three RCTs (n = 158) met inclusion criteria for quantitative synthesis. The overall antidepressant effect size of minocycline compared to placebo was − 0.78 [95% confidence interval − 0.4 to − 1.33 (P = 0.005)], indicative of a large and statistically significant antidepressant effect. Heterogeneity of the pooled sample was moderate (I2 = 62%). There was no statistically significant difference in reported adverse effects or all-cause discontinuation in the minocycline group compared to placebo (p = 0.16).

Limitations
The small number of published RCTs, small sample sizes, heterogeneity of included studies, and potential publication bias were significant limitations.

Conclusions
Overall, a large antidepressant effect was observed for minocycline compared to placebo with good tolerability. The current analysis provides a proof-of-concept for the antidepressant effects of minocycline and provides impetus for future larger RCTs as well as identification of subgroups more likely to benefit from this intervention.

https://www.sciencedirect.com/science/article/pii/S0165032717319985

 

[Logan-]

I've actually used minocycline for 6 days now. 100mg each day, plan on dropping it to 50mg for maybe one more week. Noticed that digestion has greatly improved. Used to have unpleasant diarrhea, gas, and rumbling stomach after eating sometimes, but that has totally vanished. Also, bowel movements were larger in diameter after taking the minocycline (reducing some inflammation in the intestine?). Previously, I also sometimes had adrenaline symptoms after eating (cold nose), which I suspected were caused by endotoxin, but that has vanished as well. So it seemed to have been a good experiment. (If one is going to use any antibiotic, read about possible side effects. For example, for minocycline, there is something called "intracranial hypertension". )

I got it scripted from my doc for acne. I started using it about 5 days ago. I discovered it has balanced out my hormones. Made my gut feel like it was bullet proof. No signs of estrogen dominance. My muslces feel firm, my chin feels sharp, high body temps, it has lifted my mild depression and anxiety.

My adrenal glands are also healing. I do not lose sodium anymore. I drank about 3 litres of liquid yesterday (OJ, apple juice, milk) and went to the toilet 3 times. As opposed to 6 to 7 trips per day (with an uncomfortable nudging feeling in my bladder telling me to go all the time).

After trying to fix adrenal problems for so long, I am starting to see progress with Minocycline. It has made me realise how toxic my gut must've been

Effects of Minocycline on Changes in Brain Tryptophan Metabolism and the Behavior of Juvenile Mice Elicited By Inescapable-Predator Stress.

Hideki Miura, Yu Ando , Yukihiro Noda, Norio Ozaki, Kenichi Isobe.
https://www.scitechnol.com/2324-8947/2324-8947-2-107.pdf
​

"Conclusion: Minocycline counteracted the stress-induced KYN [kynurenine] pathway and behavioral changes and attenuated the influence of early-life trauma."

​

"Because prolonged behavioral and neurochemical changes elicited by PTEs [potentially traumatizing experiences] in early life are known to become more severe in response to stress exposure in adulthood, these changes may suggest vulnerability and a predisposition to psychiatric disease such as depression and anxiety disorder including PTSD. Our present results suggest that minocycline counteracted the activation of the brain KYN pathway and the behavioral disinhibition elicited by inescapable-predator stress exposure in juvenile mice. Thus, minocycline may become a candidate drug to prevent the adult onset of psychiatric disease after exposure to PTEs such as child abuse (physical abuse, psychological abuse, and sexual abuse), neglect, infection, pain, and natural disasters." [bolds mine].

Minocyline can even treat schizophrenia

He was prescribed minocycline to treat the pneumonia and within two weeks the infection was cleared and the psychosis resolved. Minocycline was stopped and his psychiatric symptoms worsened. Treatment with the drug was resumed and within three days he was better again.

http://www.independent.co.uk/news/scien ... 69121.html

What could have happened here ?

I am guessing that his gut issues were related to low thyroid and minocyline just fixed gut issue,not the thyroid

 

[Logan-]

Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial

Olivia M Dean, Buranee Kanchanatawan, Melanie Ashton, ...
First Published June 3, 2017 Research Article
https://doi.org/10.1177/0004867417709357
Article information


Abstract
Objective:
Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder.

Methods:
A total of 71 adults with major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery–Asberg Depression Rating Scale (primary outcome), Clinical Global Impression–Improvement and Clinical Global Impression–Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au, #ACTRN12612000283875.

Results:
Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery–Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression–Improvement score – effect size (95% confidence interval) = −0.62 [−1.8, −0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score – effect size (confidence interval) = −0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score – 0.79 [−4.5, −1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [−1.7, −0.4], p = 0.017.

Conclusion:
While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.

 

[Logan-]

Minocycline Provides Neuroprotection Against N-Methyl-d-aspartate Neurotoxicity by Inhibiting Microglia
Tiina M. Tikka and Jari E. Koistinaho
J Immunol June 15, 2001, 166 (12) 7527-7533; DOI: Minocycline Provides Neuroprotection Against N-Methyl-d-aspartate Neurotoxicity by Inhibiting Microglia

Abstract
Glutamate excitotoxicity to a large extent is mediated through activation of the N-methyl-d-aspartate (NMDA)-gated ion channels in several neurodegenerative diseases and ischemic stroke. Minocycline, a tetracycline derivative with antiinflammatory effects, inhibits IL-1β-converting enzyme and inducible nitric oxide synthase up-regulation in animal models of ischemic stroke and Huntington’s disease and is therapeutic in these disease animal models. Here we report that nanomolar concentrations of minocycline protect neurons in mixed spinal cord cultures against NMDA excitotoxicity. NMDA treatment alone induced microglial proliferation, which preceded neuronal death, and administration of extra microglial cells on top of these cultures enhanced the NMDA neurotoxicity. Minocycline inhibited all these responses to NMDA. Minocycline also prevented the NMDA-induced proliferation of microglial cells and the increased release of IL-1β and nitric oxide in pure microglia cultures. Finally, minocycline inhibited the NMDA-induced activation of p38 mitogen-activated protein kinase (MAPK) in microglial cells, and a specific p38 MAPK inhibitor, but not a p44/42 MAPK inhibitor, reduced the NMDA toxicity. Together, these results suggest that microglial activation contributes to NMDA excitotoxicity and that minocycline, a tetracycline derivative, represents a potential therapeutic agent for brain diseases.

Activation of the N-methyl-d-aspartate (NMDA)3 receptors to a large extent mediates the glutamate excitotoxicity and neuronal death in several neurodegenerative diseases and ischemic stroke (1, 2, 3). Subsequent to activation of NMDA receptors occurs toxic calcium influx, which activates numerous enzymes, including neuronal NO synthase (NOS). NO is able to further increase the excitotoxicity by enhancing glutamate release from presynaptic neurons (4, 5) and inhibiting glial glutamate transporters (6, 7).

Several studies have suggested that inflammation, involving nonneuronal cells such as infiltrating leukocytes and parenchymal microglia, contributes to the delayed enlargement of ischemic brain injury (1, 2, 8), amyloid-induced neurotoxicity in Alzheimer’s disease (9, 10), and demyelination in multiple sclerosis (11, 12). The key players in inflammation are glial cells, both astrocytes and microglia, which are activated in these brain diseases and in response to glutamate excitotoxicity (13, 14, 15). Activated microglia release a large variety of neurotoxins, including the free radicals hydrogen peroxide, superoxide, and NO, that also is able to nitrate proteins; glutamate and quinolinic acid; extracellular proteases; eicosanoids; and cytokines, such as TNF-α and IL-1β, which further increase microglial proliferation and activation, thereby increasing the release of microglial toxins (8, 13, 14, 16, 17). Importantly, several studies have shown that the neurotoxicity of microglial toxins is mediated through the NMDA receptor (NMDAR), involving either glutamate and quinolinic acid or a still uncharacterized NMDAR binding molecule (18, 19, 20, 21). Because inflammation is a delayed and prolonged response to brain injury, it is regarded as a tempting pharmacological target with a potentially wide therapeutic window, unlike NMDAR antagonists that must be delivered immediately after a brain insult and have strong side effects (2, 22, 23).

We have previously shown that minocycline, a semisynthetic tetracycline derivative, is able to provide neuroprotection against global ischemia in gerbils and focal brain ischemia in rats (24, 25). In addition, minocycline delays mortality in a transgenic mouse model of Huntington’s disease (26). In all these studies, the protective effect of minocycline was associated with reduced activation of inducible NOS and IL-1β-converting enzyme, which are mainly expressed by microglia. In addition, ischemia-induced proliferation of microglia was inhibited by minocycline. In the present study, we show that NMDA-induced neuronal death involves proliferation and activation of microglial cells and that minocycline prevents completely the NMDA toxicity and the preceding activation and proliferation of microglial cells. These results support the notion that microglial activation contributes to excitotoxic neuronal death, which can be inhibited by antiinflammatory compounds, such as minocycline.

 

[Logan-]

is it better to take tetracycline over minocycline or doxycycline? (i know theyre all tetracyclines)

I think any one of these is OK. Minocycline seems to target the nervous system more than the other two, hence why it is commonly used in studies for animal models of ALS, AD, MS, Parkinson, etc.

 

[Logan-]

prescription antibiotics were the best thing that ever happened to my 30 years of gut misery.
I know people personally who've used them daily for YEARS with great benefit and the
only way you'd get them to stop would be to peel them from their cold dead hands.

don't let anyone scare you away from using them.
don't be cavalier with their use.
Results could go either way.
This is likely good advice for any drug/med/treatment you test.

Which antibiotics do you like for resolving your gut issues?

I've used minocycline and doxycycline.
I would have tested penicillin just never got around to it.

I used them for several weeks/months.
And I continue to use them periodically as needed.
they improved everything mood, pulse/temp, energy, digestion, etc...
classic example of "if its what you need its what you need"
everything Ray discusses helped to a degree at different times along the way.
My point in posting wasn't to portray abx as the best thing ever for everyone
I posted to counter the common fear of them. If its what you need its what you need.

 

[golder]

Very interesting. Known people to use antibiotics daily for years? Wondering the safety of that, do you have any thoughts? Ray mentions toxicity of most antibiotics in high doses, which is why he recoemmends say 30-40mg of penicillin for ~4 days....so 365 days a year would worry me based on that. What're your thoughts?

 

[Logan-]

I don't know.

 

[Logan-]

Minocycline And Doxycicline And Tetra Cycline Can Cause Intracranial Hypertension

Tetracyclines Cause Mitochondrial Dysfunction

The Tetracycline Antibiotics Inhibit Mitochondrial Respiration

 

[Logan-]

So there you have it - restricting PUFA intake, or taking minocycline reverses brain aging. This is really not that surprising, minocycline has been shown in animal models to inhibit pretty much every neurodegenerative condition (MS, ALS, AD, PD, etc). Guess what they all have in common? Inflammation.

Btw, this study raises the interesting possibility of using minocycline (or other tetracyclines) or cyproheptadine to block some of the effects of already ingested PUFA. Taking aspirin as well should block the remaining.

 

[Logan-]

Very interesting. Known people to use antibiotics daily for years? Wondering the safety of that, do you have any thoughts? Ray mentions toxicity of most antibiotics in high doses, which is why he recoemmends say 30-40mg of penicillin for ~4 days....so 365 days a year would worry me based on that. What're your thoughts?

I too would like to learn about the questions you asked.

 

[Tristan Loscha]

Journal of Affective Disorders
Volume 227, February 2018, Pages 219-225

Review article
Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials
Joshua D.Rosenblat Roger S.McIntyre

Highlights
•
A large antidepressant effect was observed for minocycline compared to placebo.

•
Minocycline had good tolerability with low rates of adverse effects and discontinuation.

•
Future larger RCTs of minocycline for depression are merited.

•
Future studies should also identify subgroups more likely to benefit from minocycline.

Abstract
Background
Minocycline has been identified as a potential novel treatment for depression. The objective of the current review is to determine the overall antidepressant efficacy and tolerability of minocycline.

Methods
Completed and ongoing clinical trials of minocycline for depression (both bipolar and unipolar) published prior to September 12, 2017 were identified through searching relevant databases. Using a random-effects model, data from randomized controlled trials (RCTs) were pooled to determine the antidepressant effect size of minocycline compared to placebo. Relative risk of all-cause discontinuation was determined to assess overall tolerability.

Results
Eighteen clinical studies (including published and unpublished RCTs, open label studies, ongoing clinical trials and a case report) were identified for inclusion in the qualitative synthesis. Only three RCTs (n = 158) met inclusion criteria for quantitative synthesis. The overall antidepressant effect size of minocycline compared to placebo was − 0.78 [95% confidence interval − 0.4 to − 1.33 (P = 0.005)], indicative of a large and statistically significant antidepressant effect. Heterogeneity of the pooled sample was moderate (I2 = 62%). There was no statistically significant difference in reported adverse effects or all-cause discontinuation in the minocycline group compared to placebo (p = 0.16).

Limitations
The small number of published RCTs, small sample sizes, heterogeneity of included studies, and potential publication bias were significant limitations.

Conclusions
Overall, a large antidepressant effect was observed for minocycline compared to placebo with good tolerability. The current analysis provides a proof-of-concept for the antidepressant effects of minocycline and provides impetus for future larger RCTs as well as identification of subgroups more likely to benefit from this intervention.

Efficacy and tolerability of minocycline for depression: A systematic review and meta-analysis of clinical trials - ScienceDirect

Minocycline is associated even after short term 10 day application with non reversible toxic Thyroiditis,which presents itself as hypothyroidism.Users beware.

 

[CoconutEffect]

Source?

 

[Tristan Loscha]

Source?

A member posted a similar one iirc,but in the general flow of a thread.For better visibility:

Severe And Persistent Thyroid Dysfunction Associated With Tetracycline-Antibiotic Treatment In Youth