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Minocycline For Depression: Antibiotics As Antidepressants?

Minocycline is a broad-spectrum antibiotic of the tetracycline classification, indicating that its chemical structure consists of 4 hydrocarbon rings.  The fact that minocycline has a broad-spectrum mechanism indicates that it targets a wide-range of pathogenic (Gram-positive and Gram-negative) bacteria.  In fact, when compared to other tetracycline drugs, minocycline is regarded as having the “broadest spectrum” in its effect; rather than acting like a smart-bomb, minocycline is more like an atomic (in terms of bacterial targeting).

Unlike most other tetracycline antibiotics, minocycline is highly lipophilic (fat soluble) which facilitates superior absorption, tissue distribution, and CNS infiltration (by comparison).  The drug is commonly prescribed for the management of acne and bacterial meningitis, plus is often regarded as a preferred treatment for Lyme disease due to the fact that it readily penetrates the blood-brain-barrier (BBB).

Emerging evidence suggests that minocycline may also effectively treat major depression, possibly resulting (in part) from its ability to attenuate proinflammatory cytokines.  Assuming additional robustly-designed studies are able to showcase the antidepressant efficacy of this broad-spectrum, dated antibiotic (synthesized in 1966), it may be prescribed more frequently as an antidepressant.  Moreover, it may encourage pharmaceutical companies to consider reengineering and/or pioneering selective, narrow-spectrum antibiotics specifically for neuropsychiatric conditions.

How Minocycline May Treat Depression (Mechanisms)

The multimodal mechanism by which minocycline treats depression isn’t fully understood.  However, a considerable amount of the scientific literature indicates that it provides an antidepressant effect primarily via reduction of inflammation.  Other mechanisms that may contribute to its antidepressant efficacy include: modulation of HPA axis, alteration of nitric oxide synthase, increasing dopamine – and possibly through elimination of pathogenic bacteria.

Anti-inflammatory: Arguably the most prominent mechanism by which minocycline treats depression is by reducing inflammation.  Minocycline decreases inflammation by inhibiting the activation of microglia, or immune cells within the CNS that remove damaged cells through phagocytosis.  Chronic microglial activation occurs when immune T cells are deployed and stimulate the microglia.

This triggers the release of proinflammatory cytokines such as INF-alpha, and when left unchecked for an extended duration, it takes a toll on the CNS.  Chronic inflammation is directly associated with ongoing activation of microglia (as induced by the T cells).  To attenuate the inflammatory response, minocycline disrupts signaling of T cells to activate the microglia, which in turn reduces proinflammatory cytokine biomarkers such as NF-kappa B, INF-alpha, IL-1B, etc.

Antioxidant effect: Although minocycline may decrease oxidative stress indirectly as a result of its anti-inflammatory effect, it may also act directly as an antioxidant by scavenging free radicals.  A publication from 2005 documents minocycline as being on par with vitamin E in terms of its ability to reduce oxidative stress.  An accumulation of oxidative stress is directly associated with neuropsychiatric disorders and neurodegenerative outcomes for numerous reasons including mitochondrial dysfunction.

In animal models, minocycline appears to significantly attenuate Japanese Encephalitis-induced neuronal damage primarily by inhibiting oxidative stress. Later research suggested that minocycline may act specifically as a scavenger of peroxynitrite (PON), a reactive oxygen species capable of damaging neurons and the blood-brain-barrier.  Its ability to scavenge some peroxynitrite may be a key mechanism by which it decreases oxidative stress to improve mood and cognitive function of those with depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16033424
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19428790
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21081502

Individuals with depression and other neuropsychiatric disorders tend to exhibit not only inflammation (and oxidative stress, neuronal damage, etc. – resulting from the inflammatory response), but also chronic activation of microglia.  Minocycline happens to be a robust microglial inhibitor which facilitates its anti-inflammatory response.  It could be speculated that minocycline may target the inflammatory aspect of depression to a greater extent than other agents.

Dopamine increases: In learned-helplessness models of depression, turnover of serotonin appears greater in certain regions such as the orbitofrontal cortex and expression of BDNF (brain-derived neurotrophic factor) is downregulated within the hippocampus.  Although conventional serotonergic antidepressants are capable of correcting these abnormalities, minocycline doesn’t appear to elicit a similar effect.  Rather than reversing these aforestated pathological features, minocycline appears to improve mood by increasing dopamine concentrations within the amygdala.

Animal models exhibiting low dopamine concentrations within the amygdala tend to avoid partaking in voluntary activities.  This could perhaps be interpreted as a reduction in motivation and/or anhedonia.  Though extracellularly high dopamine in the amygdala may be associated with stress, it is important to consider that amygdalar modification of dopamine may be associated with an antidepressant effect.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21967886

Eliminates pathogenic bacteria: Of all the literature examined, I’ve yet to find a publication suggesting that a possible mechanism by which minocycline may improve mood is through elimination of pathogenic gut bacteria. There’s increasing evidence suggesting that intestinal microbiota send signals to the brain, chiefly via the vagus nerve.  These signals differ based on the populations of specific bacteria within the gut.

If pathogenic bacteria are dominant within the intestinal lining, the crosstalk between a person’s ENS (enteric nervous system) and CNS (central nervous system) will be markedly different than someone with a dominance of probiotics.  The intestinal microbiota sends signals to the brain in multiple ways, but primarily through the vagus nerve.  If a person’s gut is overtaken by pathogenic bacteria, expect vagal tone to be altered when compared to a microbiota dominated by probiotics (healthy bacteria).

Pathogenic bacteria are capable of significantly altering a person’s neural footprint to perpetuate states of depression, anxiety, and stress.  They alter cerebral blood flow, modify neurotransmission, shift regional activation, and deliver a set of neuropeptides completely distinct from probiotics.  Although minocycline will surely not benefit someone with a “healthy gut” in terms of mood or cognitive function, it will likely bolster healthy ENS to CNS signaling among those harboring an abundance of gut pathogens.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23910373

HPA axis modulation: Many people with depression and anxiety exhibit dysregulation of the HPA (hypothalamic-pituitary-adrenal axis).  This HPA dysregulation can be caused directly as a result of neuroinflammation (from the release of proinflammatory cytokines such as TNF-alpha, as well as concurrent oxidative stress).  Although minocycline doesn’t directly act upon the HPA axis, its anti-inflammatory effect seems to indirectly reduce reactivity of the HPA axis.

Studies have shown that in humans, depressive symptoms are associated with a prolonged activation of the HPA axis.  This activation leads to the secretion of glucocorticoids such as cortisol (as a result of ACTH stimulation) and may exacerbate symptoms of depression and/or stress.  Minocycline essentially reduces HPA reactivity and overall activity as a result of its ability to reduce cytokines.

Hippocampal modulation: Another region of the brain that’s commonly studied among those with depression is the hippocampus.  Depressive individuals tend to have increased concentrations of inflammatory biomarkers (TNF-alpha and IL-1Beta) as well as IDO (indoleamine 2, 3-dioxygenase), an enzyme responsible for metabolizing L-Tryptophan.  Inflammation and IDO are inherently linked and can damage hippocampal neurons, decrease serotonin levels, and alter neurotrophins.

Administration of minocycline appears to reduce inflammation and IDO, thereby protecting hippocampal neurons from damage.  This effect also reduces enzymatic activity of IDO, allowing serotonin concentrations to remain normative.  By restoring hippocampal function and protecting neurons from inflammation, neurotrophic factors such as BDNF may return to sufficient levels to improve mood.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25907742

Neuroprotective effects: There’s considerable evidence suggesting that minocycline functions as a neuroprotective agent and possible neurorestorative.  In other words, it protects the brain from neurodegeneration and may be capable of restoring healthy neurological function if administered in a timely manner following the incurrence of damage.  The neuroprotective effect is associated with the combination of its anti-inflammatory and anti-oxidative properties, but also elicited through independent mechanisms.

One important mechanism by which minocycline preserves neural function may result from its ability to inhibit the inflammatory enzyme known as “5-lipoxygenase” (5-LOX).  CNS neurons expressing 5-LOX are thought to facilitate neurodegenerative processes and expedite brain aging – killing brain cells at a faster rate.  How would a neuroprotective and/or neurorestorative effect benefit those with major depression?

Considering that various cases of depression may result directly from neurodegeneration (internal damage) and that minocycline is capable of attenuating this damage, it makes logical sense to hypothesize that certain individuals will reap an antidepressant effect directly from this neuroprotective mechanism.  Preliminary evidence indicates that minocycline may reduce neurodegeneration among those with: Alzheimer’s disease, HIV, Huntington’s disease, multiple sclerosis, Parkinson’s disease, rheumatoid arthritis, and schizophrenia.  Therefore, it is necessary to consider that neuroprotection, coupled with possible neurorestoration, may improve functional outcomes among those with depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20169778
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19110059
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22198699
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/16712806

Nitric oxide synthase inhibition: An important possible antidepressant mechanism of minocycline that is often overlooked is its ability to inhibit the enzyme nitric oxide synthase, specifically the inducible form (iNOS).  Inducible nitric oxide synthase is responsible for facilitating the synthesis of nitric oxide (NO), a relatively benign free-radical and important signaling molecule implicated in an array of neurophysiological processes.  Nitric oxide exhibits vasodilatory effects and reduced levels of nitric oxide production are considered protective.

Preliminary evidence from animal studies indicate that inhibition of nitric oxide synthase (NOS) appears to facilitate behavioral antidepressant effects.  Human research among those with depression and anxiety have documented abnormally high concentrations of nitric oxide compared to healthy individuals.  What’s more, already-approved antidepressants such as Celexa, Imipramine, Paxil, and Stablon have been shown to inhibit hippocampal NOS with localized application.

By acting as an inhibitor of iNOS, (and potentially modulator of eNOS and nNOS), minocycline may improve mood by targeting nitric oxide.  By altering nitric oxide concentrations, minocycline will have indirectly affected extracellular concentrations of serotonin, dopamine, GABA, and glutamate – as well as the serotonin transporter (SERT).  These downstream effects of NOS modulation may contribute to minocycline’s antidepressant efficacy.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8943052
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18839024
  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991030/

Reduces microglial activation:  There is substantial evidence suggesting that microglia are chronically activated among individuals with depression.  Those with depression often exhibit structural and functional impairments of microglia.  These impairments are incurred as a result of numerous influences including: autoimmunity, infections, neurodegeneration, trauma, stroke, stress, etc.

In fact, some researchers have gone as far as to hypothesize that various forms of depression are likely a microglial disease.  These researchers propose that administration of a microglial inhibitor or stimulator may be of therapeutic benefit to those with depression as a result of microglial abnormalities.  Minocycline is a drug that functions as a microglial inhibitor, possibly another way by which it alleviates depressive symptoms.

Analyses of microglia among those who commit suicide reveal heightened activation.  Abnormally heightened and/or ongoing microglial activation facilitates the generation of proinflammatory cytokines, as well as affects function of neurons and synapses.  Since minocycline reduces polarization of microglia to M1 (inflammatory states), depressive symptoms are less likely to ensue.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26442697

Note: It remains unclear as to which of the aforestated mechanisms facilitates most of minocycline’s antidepressant effect.  It should be considered that all factors contributing to varying degrees, possibly contingent upon the specific causative underpinnings of a person’s depression.  Someone with depression caused primarily by inflammation may derive most of the benefit from the anti-inflammatory effect of minocycline, whereas an individual with a genetic polymorphism of an NOS gene may reap more benefit from its ability to inhibit iNOS.

Benefits of Minocycline for Depression (Possibilities)

There are numerous potential benefits to be attained from using minocycline as an antidepressant.  It provides an alternative set of antidepressant mechanisms from standard pharmacology and may be useful for treating depression resulting from inflammation or microglial dysfunction.  Furthermore, minocycline appears to be well-tolerated and may act synergistically with conventional antidepressants to significantly improve mood.

  • Adjuvant intervention: Minocycline may be an effective adjunct to a first-line antidepressant such as an SSRI in partial responders. Those who are getting some symptomatic relief from an SSRI may wish to test the concurrent administration of minocycline to determine whether it provides benefit.  Since minocycline’s mechanism of action involves targeting inflammation, oxidative stress, nitric oxide, microglia, etc. – it may complement the effects of a serotonergically-based intervention.
  • Alternative option: There’s evidence to suggest that many people who pursue antidepressant treatment fail to respond to first-line options. Some individuals try drug-after-drug, essentially playing “antidepressant roulette” with their help of a medical professional.  Unfortunately, constant jumbling of neurotransmission as a result of ineffective approaches may even increase depression and suicidality.  For this reason, there is an increasing need for alternative options with distinct mechanisms from monoaminergic modulators.  Minocycline appears to possess an alternative mechanism of action with a favorable safety profile, making it worthy of consideration among patients with refractory depression.
  • HIV depression: The depression that often results following contraction of HIV/AIDS is multifaceted, but may stem predominantly from viral replication. Viral replication activates T cells, which in turn leads to upregulation of proinflammatory cytokines.  Proinflammatory cytokines can cause depression, especially at abnormally high concentrations.  Minocycline inhibits HIV replication in the CNS and blunts T cell activation, making it a potential antidepressant and neuroprotective for those with HIV.
  • Inflammation-induced depression: The associations between inflammation and neuropsychiatric disorders are ubiquitous. Fortunately, minocycline is capable of significantly decreasing inflammation.  Those with depression caused mostly by inflammation may find that minocycline significantly enhances mood.  A reduction in inflammation throughout the body may also improve general health.
  • Long-term effect: It is unclear as to whether minocycline provides long-term antidepressant efficacy. However, for conditions such as MS (multiple sclerosis), long-term administration of minocycline over a 24-month period was associated with sustained improvements.  Therefore, it could be speculated that minocycline remains neurophysiologically efficacious even after a long-term.  Since many antidepressants stop working due to tolerance, minocycline may be a superior option.
  • Neuroprotective effect: Depression is known to cause neurodegeneration when left untreated for a sustained duration. Intervention with minocycline may not only alleviate depressive symptoms, but it could protect the brain from damage associated with oxidative stress, inflammation, viruses, and immune activity.  There’s ample evidence to suggest that minocycline preserves dopaminergic neurons and transporters, as well as decreases 5-LOX – a biomarker associated with brain aging.
  • Psychotic comorbidities: Studies of individuals with diagnoses of major depression with psychotic features, as well as schizophrenia, reveal that minocycline not only attenuates some depression, but also the psychotic features. It doesn’t appear to work particularly well for positive symptoms (e.g. hallucinations, delusions, etc.), but addresses some of the negative symptoms (e.g. motivational deficits, anhedonia, etc.).  Since cases of psychotic depression are often extremely difficult to treat, minocycline may add to the paucity of effective interventions for partial- and non-responders.
  • Refractory depression: Individuals struggling with refractory depression generally derive no benefit from traditional antidepressants. For this reason, they need an agent (or combination of agents) that modulate a unique set of neurophysiological processes.  Minocycline alters nitric oxide, reduces inflammation, decreases free radical concentrations, etc.  When paired with an SSRI (or other antidepressant), the culmination of neuromodulatory effects may alleviate resistant cases of depression.
  • Tolerability: Several studies note that, in terms of tolerability, minocycline is about as well-tolerated as a placebo. This indicates that minocycline is unlikely to cause significant unwanted side effects.  Although minocycline is not devoid of side effects (no drug is), it may not cause unwanted effects such as weight gain or sexual dysfunction.  No significant adverse effects have been documented among those taking it for depression.

Drawbacks of Minocycline for Depression (Possibilities)

Before you assume that minocycline is some utopian, panacea-like intervention for depression, just know that there are some possible drawbacks.  Not only could minocycline induce neurodegeneration among select populations (e.g. ALS patients), it may exacerbate depressive symptoms via elimination of healthy gut flora and/or inhibiting microglia.  These drawbacks should be considered before minocycline is pursued or administered with the intention of treating depression.

  • ALS patients: Individuals with the neurodegenerative condition ALS (amyotrophic lateral sclerosis) exhibit faster neurodegeneration when taking minocycline at dosages up to 400 mg/day for 9 months.  This was evidenced by a relatively large-scale randomized, controlled trial with over 400 patients.  It is unclear as to how those with ALS are detrimentally affected by minocycline, but exacerbation of neurodegeneration can occur among these patients. (Source: http://www.ncbi.nlm.nih.gov/pubmed/17980667).
  • Eliminates healthy gut bacteria: Though minocycline is capable of obliterating pathogenic intestinal bacteria, its classification as a broad-spectrum antibiotic indicates that it is equally as likely to eradicate healthy intestinal bacteria. Elimination of healthy gut bacteria is associated with unhealthy ENS (enteric nervous system) functioning, as well as suboptimal ENS to CNS communication.  The implications associated with killing the entire microbiota may be deleterious – especially over a long-term.
  • Side effects: Minocycline is highly lipophilic (or fat-soluble), a characteristic allowing it to penetrate the CNS (and blood-brain-barrier) with relative ease compared to other tetracycline antibiotics. However, this CNS penetration is associated with potentially unwanted side effects including: autoimmunity, dizziness, drowsiness, headaches, nausea, skin discoloration, stomach aches, vomiting.  Some individuals may struggle to tolerate minocycline, especially at high doses and/or over a long-term.
  • Unknown long-term outcomes: Preliminary evidence suggests that minocycline is likely to be fairly well-tolerated, even over a long-term. However, the long-term efficacy, safety, and tolerability among those with neuropsychiatric conditions isn’t understood.  Hypothetically, some individuals may experience short-term mood enhancement from minocycline, but notice a relapse in depressive symptoms over a longer-term of administration.
  • Questionable efficacy: At the moment, the therapeutic efficacy of minocycline for the treatment of depression should be considered questionable. No large scale, randomized controlled trials (RCTs) have been conducted with minocycline to support its usage as a clinical intervention.  Until minocycline is proven effective with larger-scale studies, only antidepressants and/or adjuncts that have been validated with robust science should be utilized.
  • Worsening of depression: It is plausible to assume that not everyone will respond to minocycline for the treatment of depression. In fact, there’s evidence that with long-term administration, minocycline may trigger autoimmunity and/or modulate microglial activation in such a way that depression worsens.  A subset of depressive individuals are thought to exhibit underactive microglia, and for these persons, a microglial inhibitor such as minocycline should be avoided.

Minocycline for Depression (Review of Literature)

Included below is a synopsis of the scientific research discussing the antidepressant efficacy of minocycline.  A bulk of the literature suggests that minocycline is likely capable of improving depressive symptoms.  That said, a small amount of evidence suggests that minocycline may provide insignificant therapeutic benefit.  Minocycline didn’t receive much attention as a possible antidepressant until 2008, and as a result, it took several years before newer studies reevaluated its effect on mood.

2016: 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.

A study published by Majidi et al. (2016) documented the effect of minocycline on neonatal immune activation in adult mice.  There is ample evidence to suggest that neonatal infections (leading to immune activation) increase risk of developing a neuropsychiatric disorder such as major depression.  One mechanism by which neonatal infections may induce neuropsychiatric abnormalities is via dysregulation of the HPA (hypothalamic-pituitary-adrenal) axis.

Preliminary evidence indicates that the antibiotic minocycline is capable of treating depression by inhibiting activation of microglia.  Microglia are considered resident immune cells within the CNS that typically respond to neuronal damage and remove damaged cells via a process known as phagocytosis.  However, chronic activation of microglia induces neuronal damage by facilitating the release of cytotoxic molecules – leading to inflammation and oxidative stress.

In this particular study, researchers investigated whether minocycline would reduce neonatal immune activation that causes HPA dysregulation, and ultimately depression, at a later point an animal’s (mouse’s) lifetime.  When mice were in a neonatal phase of development, they were administered either lipopolysaccharide or saline on days 3 to 5.  During lactation they were administered dams (days 6 to 20), and later during adolescence, they received either: minocycline or water from drinking bottles.

Researchers assessed depression and anxiety behaviors, reactivity of the HPA axis, and hippocampal inflammation (TNF-alpha and IL-1Beta).  In all cases, the neonatal immune activation increased propensity of depressive and anxious behavior onset in adulthood.  Moreover, HPA axis activity was classified as “hyperactive” and inflammatory biomarkers (TNF-alpha and IL-1Beta) within the hippocampus were high.

Administration of minocycline significantly decreased neurophysiological abnormalities in adult mice that were exposed to neonatal inflammation.  Furthermore, minocycline had no detrimental effect upon behavior, HPA axis activation, nor hippocampal inflammation.  Researchers note that minocycline administration during early development may reduce likelihood of neurophysiological and/or behavioral abnormalities in adulthood.

Although it is unclear as to whether minocycline exerts similar effects in humans, preliminary evidence indicates that it may.  Investigations in humans are warranted to determine whether minocycline may effectively prevent neuropsychiatric complications that arise following early-life infections, microglia activation, and/or inflammation.  It remains unclear as to whether minocycline necessitates ongoing administration to maintain benefit.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26521068

2016: Therapeutic effects of minocycline on mild-to-moderate depression in HIV patients: a double-blind, placebo-controlled, randomized trial.

A study by Emadi-Kouchak et al. (2016) documented the effect of minocycline on depression associated with HIV (human immunodeficiency virus).  It is understood that HIV takes a serious psychological toll on those diagnosed.  Not only may individuals with HIV experience depression over the fact that they have a highly-stigmatized, incurable condition, but there’s evidence that the virus itself inflicts damage upon the CNS.

The damage inflicted by HIV upon the CNS may cause neuropsychiatric conditions in itself, leading to feelings of depression and anxiety.  Since those with HIV are at elevated risk of developing depression, researchers endeavored to determine whether minocycline may exhibit antidepressant effects in this targeted-population.  For the study, researchers recruited 46 patients diagnosed with HIV with comorbid mild-to-moderate depression severity.

They set up a double-blind, placebo-controlled, randomized, parallel trial and assigned patients to receive 6 weeks of treatment with minocycline (100 mg, b.i.d.) or a placebo.  To gauge efficacy of the interventions, researchers assessed depressive symptoms with the Hamilton-Depression Rating Scale (HDRS) prior to the interventions (at baseline), after 3 weeks of treatment, and after the full 6-week term.  Results indicated that administration of 100 mg minocycline (b.i.d.) improves symptoms of depression among patients with HIV.

Moreover, there were no significant differences in reported adverse effects and no major side effects were documented.  This suggests that minocycline may be an effective intervention for attenuating depressive symptoms among populations with HIV.  It is unclear as to whether the intervention is effective over a longer-term and/or if it improves those with severe cases of depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26465919

2016: Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

A study from 2016 by Vogt et al. tested the tetracycline antibiotic minocycline for the treatment of depression and anxiety among C57BL/6 mice.  Their impetus for testing minocycline was based on the fact that preliminary evidence suggested that it may be a novel treatment for various neuropsychiatric disorders, with a multimodal mechanism of action.  They noted that prior to their research, evidence to support the antidepressant efficacy of minocycline in animal models was mixed; some studies noted benefit, while others noted no effect.

In their study, researchers administered minocycline (20-40 mg/kg, intraperitoneal injection), diazepam (0.5 mg/kg), or imipramine (20 mg/kg) to C57BL/6 mice and compared behavior on depression and anxiety tests.  The tests included: Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test, and Openfield Test.  Contrary to their hypothesis, researchers discovered that mice treated with minocycline exhibited no antidepressant or anxiolytic behavioral changes compared to mice receiving imipramine (a tricyclic antidepressant) or diazepam (a benzodiazepine anxiolytic).

Results from this study convey that minocycline doesn’t improve depressive nor anxious symptoms among C57BL/6 mice.  This suggests that therapeutic benefits of minocycline may be contingent upon the specific strain of mice to which it is administered.  Moreover, this provides evidence suggesting that minocycline may lack the antidepressant and/or anxiolytic efficacy reported in other studies.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26698398

2015: Minocycline treatment ameliorates interferon-alpha- induced neurogenic defects and depression-like behaviors in mice.

A study conducted by Zheng et al. (2015) noted that the agent Interferon-alpha (IFN-alpha) is a proinflammatory cytokine that is administered to treat chronic hepatitis and malignancy.  It stimulates the immune system, carries antiviral properties, and inhibits proliferation of cancerous cells.  Long-term administration of IFN-alpha is associated with onset of clinical depression, making the treatment a catch-22; treat the hepatitis, but feel extremely depressed in the process.

Previous research indicates that one way by which IFN-alpha may cause depression is by inhibiting hippocampal neurogenesis.  Inhibition of hippocampal neurogenesis induces depression in adult mice and humans as a result of stimulating endogenous microglial IFN-alpha secretion.  This endogenously secreted IFN-alpha suppresses hippocampal neurogenesis and contributes to depression.

Researchers noted that after 5-weeks of IFN-alpha treatment, adult mice exhibited an upregulation in proinflammatory cytokines and markedly decreased hippocampal neurogenesis.  However, concurrent administration of minocycline attenuated proinflammatory cytokine production and maintained normative hippocampal neurogenesis.  Results indicated that minocycline significantly reduced depressive behavioral tendencies in mice following IFN-alpha treatment.

The results of this study indicate that minocycline administration may inhibit IFN-alpha-induced depression by reducing microglial activity.  Among those experiencing depression following and/or during IFN-alpha treatment, minocycline may treat the root cause.  For those who fail to respond to first-line serotonergic (SSRI) antidepressants, minocycline may be a helpful intervention.

It should be noted that first-line antidepressants can stimulate hippocampal neurogenesis and also reduce microglial inflammation.  That said, minocycline may be more effective in attenuating microglial activation than conventional antidepressants.  In any regard, further human research is warranted, particularly among those with depression stemming from IFN-alpha.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25674053

2015: Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomized controlled trial.

A study presently underway by Husain et al. (2015) notes that major depression is a leading cause of disability throughout the world.  It also mentions that a significant number of individuals pursuing pharmacological treatment for depressive disorders fail to derive therapeutic benefit.  There is emerging evidence to suggest that targeting inflammation may be an effective way to treat depression.

The antibiotic drug minocycline is capable of reducing inflammation and is one of few tetracycline antibiotics that adequately penetrates the CNS enough to affect the brain.  Evidence from open-label trials indicates that minocycline is an effective antidepressant augmentation strategy among those who fail to derive sufficient symptomatic relief.  To further investigate the adjuvant potential of minocycline, researchers organized a 3-month, double-blind, placebo-controlled, pilot study.

For the study, they recruited 40 participants that had been formally diagnosed with major depression (in accordance with DSM-IV criteria).  Since the study is currently underway, it is unclear as to what the results will be.  That said, researchers will be assessing participants with the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression (CGI) scale, Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder scale (GAD-7).

Researchers will also collect data regarding side effects and inflammatory cytokine biomarkers.  The regimen of minocycline being utilized as an antidepressant adjunct is 100 mg once daily for 2 weeks, and 200 mg once daily thereafter.  Though the study isn’t complete, researchers hypothesize that adjunct minocycline treatment may attenuate depressive symptoms to a greater extent than a standalone antidepressant.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26374703

2015: Minocycline Attenuates Depressive-Like Behavior Induced by Rat Model of Testicular Torsion: Involvement of Nitric Oxide Pathway.

A study by Saravi et al. (2015) mentioned that testicular torsion, or rotation of testicles to the extent that blood flow is restricted, causes pain, swelling, and depression in humans.  This particular study aimed to determine the psychological effect of testicular torsion in animal models and test the antidepressant efficacy of minocycline on testicular torsion-induced depression.  They speculated that one such antidepressant mechanism associated with minocycline may be via modulation of nitric oxide (NO)/cyclic GMP pathways.

A unilateral testicular torsion was induced in 36 rats and thereafter, minocycline was injected as a standalone agent or concurrently with various agents that alter nitric oxide including: nitro-l-arginine methyl ester (1-NAME), aminoguanidine (AG), l-arginine, or sildenafil.  Researchers recorded locomotor function in an open field-test and immobility of rats in a forced swimming test (FST).  After 30 days of functioning with the testicular torsion, testosterone and serum nitrite concentrations were measured in the rats.

Researchers noted a correlation between lower plasma testosterone OR increased serum nitrite WITH prolonged immobility in the forced swim test.  Administration of minocycline at 160 mg/kg per day elicited the most pronounced antidepressant effect in the rats dealing with the testicular torsion.  This antidepressant effect was evidenced by reduced immobility in the forced swim test.

Results indicated that when minocycline 80 mg/kg was combined with L-NAME (10 mg/kg) or AG (50 mg/kg), a significant antidepressant response was also observed.  Based on tehse results, researchers speculated that the NO/cGMP pathway was implicated in testicular torsion-induced depression among the rats.  They note that one mechanism by which minocycline likely attenuates depressive symptoms is via modulation of nitric oxide.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26381433

2015: On the effect of minocycline on the depressive-like behavior of mice repeatedly exposed to malathion: interaction between nitric oxide and cholinergic system.

A study by Saravi et al. (2015) was conducted to determine the antidepressant effects of minocycline in animal models.  The depression was induced as a result of exposure to malathion, an organophosphate insecticide.  Researchers hypothesized that the nitric oxide/cGMP pathway may be implicated in the onset of depression following exposure to the malathion.

In the study, mice were slated to receive malathion once per day for a full week.  Following the onset of depression, minocycline was administered via intraperitoneal injection either a standalone or along with agents that modulate nitric oxide systems.  Examples of such nitric oxide modulators included L-NAME (a non-specific inhibitor), AG (a specific inhibitor), L-arginine (a precursor), or sildenafil (PDE5 inhibitor).

Thereafter, researchers assessed mice performance on an open-field test, forced swim test, and tail suspension test.  They also measured concentrations of nitrite within the hippocampus and activity of the enzyme acetylcholinesterase.  As expected, the results indicated a significant increase in depressive tendencies following exposure to malathion for 7 days.

However, treatment with minocycline (160 mg/kg) substantially decreased immobility in the forced swim test and tail suspension test.  Moreover, smaller doses of minocycline at 80 mg/kg combined with L-NAME (3 mg/kg) or AG (25 mg/kg) also effectively attenuated depression.  Researchers mentioned that minocycline appeared to reduce concentrations of nitrite within the hippocampus.

This study confirms an influence of the NO/cGMP pathways in depression induced via malathion exposure.  Furthermore, it appears as though minocycline’s antidepressant efficacy results from its ability to alter the same (NO/cGMP) pathway.  This suggests that the antidepressant benefit associated with minocycline may be most significant among those with NO/cGMP pathway dysfunction.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26581675

2015: TNFα mediates stress-induced depression by upregulating indoleamine 2,3-dioxygenase in a mouse model of unpredictable chronic mild stress.

A study by Liu et al. (2015) mentions that depression is often associated with exposure to stressors.  Substantial life stressors often increase propensity of an individual to become depressed, especially if stressors are chronic.  Ongoing stress is understood to induce immune dysfunction and increase proinflammatory cytokines (e.g. TNF-alpha, IL-1Beta, etc.).

These proinflammatory cytokines are thought to contribute significantly to the pathogenesis of depression.  In this study, researchers specifically honed in on the dynamics by which proinflammatory cytokines induce depressive states and links between depression and unpredictable chronic mild stress (UCMS) in mice.  Researchers gathered 4 groups of mice and assigned them to groups: saline-control, saline-UCMS, drug-control, and drug-UCMS.

Mice were considered depressed when they exhibited a decrease in preference for sucrose and increased immobility on the TST (tail-suspension test) and FST (forced-swim test).  Various agents were administered with intraperitoneal injections, including: minocycline (30 mg/kg, daily), infliximab (10 mg/kg, b.i.w.), and 1-methytryptophan (10 mg, daily).  Biomarkers including TNF-alpha, IL-1Beta, and IL-18 significantly increased as a result of UCMS.

Administration of minocycline 30 mg/kg per day prior to the UCMS inhibited upregulation of all markers.  Depression was associated with increased TNF-alpha in both plasma and the cerebral cortex of mice.  All drugs selected for the study (minocycline, infliximab, 1-methyltryptophan) prevented pathogenesis of depression.

What’s more, the ability of these agents to inhibit TNF-alpha was considered neuroprotective in that they shielded neurons from damage associated with IDO (indoleamine 2, 3-dioxygenase).  When TNF-alpha increases (as a result of UCMS), IDO is upregulated and inflicts damage upon neurons.  Overall, it appears as though minocycline may effectively prevent onset of depression and neuronal damage associated with heightened TNF-alpha concentrations.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26083579

2015: Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients with Persistent Symptoms.

Interestingly, researchers Kelly et al. (2015) conducted a study to assess the efficacy of minocycline as an adjunct to clozapine among individuals with schizophrenia.  Patients included in this study hadn’t attained sufficient symptomatic relief from the antipsychotic clozapine, a gold-standard option for refractory cases of schizophrenia.  Despite the insufficient relief from clozapine, researchers speculated that a tetracycline antibiotic may serve as an effective adjunct.

For the study, researchers organized a 10-week, double-blind, placebo-controlled trial with 52 patients that had been diagnosed with persistent schizophrenia or schizoaffective disorder.  All 52 patients had experienced persistent positive symptoms (e.g. hearing voices, delusions, etc.).  At random, these 52 individuals were assigned to receive minocycline (100 mg, b.i.d.) or the placebo.

Prior to administration of the minocycline or placebo adjunct, measures were taken to assess positive and cognitive symptoms among participants.  Secondary measures were also taken and included: negative symptoms, avolition, anxiety/depression.  Following treatment, measures were retaken and improvement in symptomatic severity was determined.

Results indicated that minocycline had no significant effect upon positive nor cognitive impairment associated with schizophrenia.  However, the individuals that received minocycline significantly improved in anxiety/depression, avolition, and working memory.  This suggests that minocycline may alleviate non-positive symptoms associated with schizophrenia.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26082974

2014: Minocycline modulates neuropathic pain behavior and cortical M1-M2 microglial gene expression in a rat model of depression.

In 2014, a study was published by Burke et al. to investigate the effect of minocycline on depressive behavior, allodynia, genetic microglial biomarkers, and inflammatory neural markers among rats with depression.  Prior to the study, researchers highlighted links between microglia activity, neuroinflammation, chronic pain, and depressive syndromes.  For this particular investigation, researchers utilized an olfactory-bulbectomized (OB) model of depression which is known to cause hyperactivity in an open-field.

Many antidepressants are capable of treating OB-induced depression when administered chronically.  In any regard, the the acute administration of minocycline failed to ameliorate depression in the olfactory bulbectomy model, but it appeared to significantly inhibit mechanical allodynia in OB and sham rats.  When administered chronically, minocycline continued to inhibit mechanical allodynia in OB rats and also attenuated depressive behaviors; these effects were not apparent in the sham group.

Biomarker assays revealed that minocycline decreased microglial activation as evidenced by a decline in CD11b and IL-1B – in the prefrontal cortices of the sham mice.  After chronic administration of minocycline in the OB rats, expression of M2 (a microglia biomarker) and anti-inflammatory cytokine IL-10 were upregulated in the prefrontal cortex.  Other markers that had increased included IL-1B, IL-6, and SOCS3 of the OB rats.

Researchers concluded that minocycline corrects abnormal behaviors associated with neuropathic pain.  It also appears to alter microglial activity and inflammatory cytokines.  However, it was evident that the effect of minocycline was contingent upon whether the rats exhibited a non-depressive or depressive phenotype.  This suggests that the effects of minocycline may be subject to variation based on phenotypes.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24994592

2012: Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study.

A study by Miyaoka et a. (2012) noted that around 1 in 4 patients admitted to a hospital as a result of depression also exhibit psychosis.  Psychotic symptoms can occur among those with unipolar or bipolar depression and are often challenging to manage.  Researchers further mention that minocycline, a second-generation tetracycline antibiotic, appears to act as an antidepressant while simultaneously providing antioxidant, anti-inflammatory, and neuroprotective effects.

A 6-week open-label trial was organized to determine the therapeutic efficacy and safety of minocycline as an adjunct to antidepressants among 25 adults diagnosed with psychotic depression (in accordance with the DSM-IV).  At pre-treatment baseline, symptomatic severity was assessed with the Hamilton Depression Rating Scale (HAM-D) as a primary measure.  Secondary measures included the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI).

Following 6 full weeks of treatment, the HAM-D, BPRS, and CGI were readministered to detect any changes in symptomatic severity.  Results indicated that administration of minocycline (150 mg/day) along with a conventional antidepressant (Paxil, Luvox, Zoloft), significantly decreased depressive symptoms.  To put the significance in perspective, the baseline average HAM-D score was approximately 40, whereas following 6 weeks of treatment it had dropped to around 7.

What’s more, psychotic symptoms (as determined by the BPRS) had decreased significantly from an average baseline score exceeding 63, to a score of less than 5 following 6 weeks of treatment.  No significant adverse reactions or tolerability issues were encountered with the treatment.  This study provides preliminary evidence to support the adjunct usage of minocycline along with antidepressants among those diagnosed with psychotic depression.

Clearly the combination of minocycline along with an antidepressant was highly effective among the 25 adults in this particular study – scores of both depressive and psychotic symptoms plummeted within 6 weeks.  That said, the major limitation associated with this research is that it didn’t incorporate a double-blind, placebo-controlled, randomized design.  Further research is warranted to investigate the efficacy of minocycline as an antidepressant adjunct for cases of refractory and/or psychotic depression.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22349578

2012: Minocycline and aspirin in the treatment of bipolar depression: a protocol for a proof-of-concept, randomized, double-blind, placebo-controlled, 2×2 clinical trial.

Researchers Savitz et al. (2012) are currently investigating the combination of minocycline and aspirin (an anti-inflammatory) for the treatment of bipolar depression in a proof-of-concept trial.  Why this combination?  Well, individuals with bipolar disorder often exhibit neuronal and glial cell losses (e.g. brain cells are killed) and deleterious dendritic remodeling.  The culmination of these neurodegenerative alterations are thought to be a result of chronic neuroinflammation.

Chronic neuroinflammation is also associated with onset of major depression.  Since many patients diagnosed with bipolar depression are experiencing neurodegenerative alterations and aren’t responding well to standardized pharmacology, alternative interventions may prove beneficial.  For this reason, researchers chose to investigate minocycline along with aspirin.

Minocycline was chosen as a result of preliminary evidence noting its antidepressant efficacy, anti-inflammatory properties, and neuroprotective effects.  Aspirin was included in the study because it inhibits COX-1 (cyclooxygenase 1), an enzyme associated with inflammation.  Researchers want to determine whether this unconventional combination is capable of reducing depression and/or protecting the brain from damage associated with inflammation.

The trial recruited 120 patients that had fit DSM-IV diagnostic criteria for bipolar depression (either Type 1 or Type 2).  The study is designed to be randomized, double-blinded, placebo-controlled, and parallel-group with a 2×2 design.  In other words, patients will be assigned at random to receive one of four treatments: placebo-placebo, minocycline- placebo, aspirin-placebo, or minocycline-aspirin.

The dosage of minocycline set to be administered is 100 mg (b.i.d.), whereas the dosage of aspirin to be administered is 81 mg (b.i.d.).  Antidepressant efficacy will be determined based on change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from pre-treatment baseline to post-treatment (6-weeks later).  Secondary measures will include comparing baseline C reactive protein and proinflammatory cytokines.  This trial is currently in Phase 3 (at the time of this writing) – expect results to be publicized following its completion.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22357572

2012: Minocycline produced antidepressant-like effects on the learned helplessness rats with alterations in levels of monoamine in the amygdala and no changes in BDNF levels in the hippocampus at baseline.

A study by Arakawa et al. (2012) documented the antidepressant effects of minocycline when administered to learned haplessness (LH) rats, a common animal model of depression.  They administered minocycline into the cerebral ventricle of the LH rats and noted a significant antidepressant effect.  Initially researchers suspected that this antidepressant effect may have been attributed to increased locomotor activation.

However, when minocycline was administered to naïve (non-LH) control rats, no locomotor enhancement was apparent on open field tests.  When compared to the non-LH control rats, the LH-rats exhibited elevated serotonin turnover in the OFC (orbitofrontal cortex) and downregulated hippocampal BDNF (brain-derived neurotrophic factor).  Administration of minocycline had no effect on serotonin turnover in the OFC nor hippocampal BDNF.

However, it did increase dopamine (DA) levels, as well as dopamine metabolites within the amygdala.  Researchers concluded that minocycline may be a therapeutic agent for the treatment of depression.  Due to its therapeutic mechanism of action by targeting dopamine (rather than serotonin and BDNF), its efficacy may be bolstered by concurrent administration of an SSRI (which mediates serotonin and BDNF).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21967886

2012: Novel therapeutic targets in depression: minocycline as a candidate treatment.

A report by Soczynska et al. (2012) outlined the therapeutic potential of minocycline as an intervention for depression.  Authors noted that individuals diagnosed with mood disorders such as major depression often fail to derive sufficient symptomatic remission from available therapies.  The pathogenesis of depressive disorders may be subject to significant interindividual variation, but models suggest many causative underpinnings including: monoaminergic abnormalities, neuroinflammation, oxidative stress, etc.

In any regard, treatments that address at least one of the aforestated underpinnings are often efficacious in attenuating depressive symptoms.  Researchers propose that minocycline may exert an antidepressant effect by correcting a multitude of neurophysiological abnormalities associated with depression (e.g. inflammation, oxidative stress, etc.).  They discuss the need for randomized, controlled trials to evaluate minocycline’s antidepressant efficacy.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22963995

2012: Minocycline: therapeutic potential in psychiatry.

A report by Dean et al. (2012) underscores the therapeutic potential of minocycline as a psychopharmacological agent.  Researchers note that the simplistic modulation of monoamines with conventional antidepressants often yields suboptimal symptomatic remission.  Emerging evidence indicates that the pathogenesis of depression is a bit more complex than the dysfunctionality of monoamines.

This report documents possible causative factors associated with depression including: glutamatergic dysfunction, inflammation, neurotrophins, and oxidative stress.  The antibiotic minocycline was discussed as a potential antidepressant due to the fact that it is capable of inhibiting glutamatergic excitotoxicity plus reduces inflammation and exhibits neuroprotective properties.  As a result of these effects, researches proposed that minocycline may be an effective adjunct to conventional psychiatric treatments.

They discussed some evidence from small-scale trials and case studies to suggest efficacy of minocycline for various conditions including schizophrenia.  Since the data is minimal and trials haven’t been robustly designed, minocycline cannot yet be recommended as a clinical intervention.  That said, researchers hypothesized that minocycline could be a novel psychiatric agent for future use.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22486246

2008: Does minocycline have antidepressant effect?

Among the earliest publications suggesting that minocycline may exhibit antidepressant properties was by Pae et al. (2008).  These researchers noted that around 2 of 3 patients being treated for depression with a standalone antidepressant fail to derive sufficient symptomatic remission.  For this reason, they emphasized the value of exploring alternative agents with atypical mechanisms of action compared to standardized antidepressants.

One such atypical mechanism of action may involve targeting inflammation.  Major depressive disorders are associated with heightened inflammation, as well as neurodegeneration (possibly a result of unaddressed inflammation).  For this reason, researchers suggested that minocycline, a tetracycline antibiotic, may be worth investigating as an antidepressant.

Data from animal research indicates that minocycline has anti-inflammatory, neuroprotective, and antidepressant properties.  Anecdotes from humans being treated with minocycline as an adjunct to an antidepressant often reported significant benefit.  Researchers speculated that minocycline may be of significant therapeutic value to those with depression and comorbid cognitive deficits.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18267354

Limitations associated with research of minocycline for depression

There are numerous limitations associated with the currently-available research of minocycline for depression.  Notably, there are few human trials that have been conducted with large numbers of participants and/or that incorporate robust RCT designs.  Moreover, it is unclear as to whether the implications associated with long-term administration may be deleterious for select individuals.

  • Comparative efficacy: The comparative efficacy of minocycline to already-approved antidepressant options isn’t well-documented. Researchers should attempt to determine whether minocycline is as effective as various first-line options such as SSRIs/SNRIs, as well as whether it is significantly more effective in alleviating symptoms compared to a placebo.  It could be that minocycline is equally as effective as various first-line interventions for the treatment of depression.
  • Dangers (Long-Term): The dangers associated with long-term minocycline treatment may be more significant than current research portrays. Although it is known that those with ALS exhibit quicker neurodegeneration as a result of minocycline, some individuals may end up with a worsening of depression as well.  Furthermore, it is unclear as to whether minocycline may provoke autoimmunity among long-term users taking it for depression.
  • Depressive subtypes: Researchers should investigate whether minocycline is more suited to treat specific subtypes of depression than others. In other words, a patient suffering from IFN-alpha-induced depression as a result of treatment for hepatitis may derive more substantial benefit from minocycline than a conventional monoaminergic modulator.  However, someone with a non-inflammatory depressive subtype may derive less benefit from minocycline.  The particular neurophysiological features associated with depression may best predict minocycline responders.
  • Designs: An obvious problem is that most study designs investigating minocycline are not placebo-controlled, double-blinded, nor randomized. Designs that are of substandard criteria may yield misleading results.  Though results from non-placebo studies may be accurate, they necessitate validation from follow-up randomized controlled trials (RCTs).
  • Dosage: It isn’t fully clear as to what the optimal dosage of minocycline is for the treatment of depression. When used as a standalone intervention, the dosage necessary to attenuate depressive symptoms may differ compared to when used as an adjunct.  Future efforts should be made to pinpoint the therapeutic dosage range of minocycline as an antidepressant adjunct, as well as for its standalone usage.
  • Lack of human trials: There is a significant amount of research that’s investigated the efficacy of minocycline in animal models of depression. However, there’s a paucity of completed trials with human participants that have only been diagnosed with major depressive disorder (MDD).  Researchers should endeavor to increase the number of trials conducted among human participants that have been diagnosed with depression (in accordance with DSM criteria).
  • Small-scale studies: Studies with limited participant numbers may also yield misleading results. Most research conducted on humans with depression did not recruit large samples of participants.  In addition to design improvements, greater numbers of participants in future research should help elucidate the antidepressant efficacy of minocycline.
  • Special populations: Minocycline warrants investigation among special populations such as those with HIV-based depression and/or those with depression stemming from immune dysfunction. It may be that minocycline is ineffective for certain depressive subtypes such as those in which microglial activation is already inhibited and/or in which inflammation is not deemed problematic.  However, it may be more effective (compared to standard monoaminergic antidepressants) among those with chronic microglia activation, inflammation, oxidative stress, etc.  Minocycline may be better suited to address specific pathioetiological correlates of certain depressive footprints.

Based on the evidence, should minocycline be used as an antidepressant?

In the event that an individual derives insufficient relief from standardized antidepressant interventions and conventional adjuncts, minocycline warrants consideration – especially as an adjuvant.  It is relatively safe with minimal side effects, and has been tested in human trials for difficult-to-treat cases of depression.  Perhaps minocycline warrants most consideration among special populations such as those with HIV-related/induced depression, immune dysfunction-induced depression, and/or refractory depression with psychotic features.

Among standard populations with normative refractory cases of depression, minocycline should only be considered after other, more substantiated options have been pursued.  That said, many adjuvant interventions such as antipsychotics, lithium, and/or psychostimulants are not devoid of risks.  Some could argue that the dangers associated with conventional adjuncts, especially over the long-term, are not worth the risks.

Although the long-term safety of minocycline hasn’t been confirmed, it may be safer with greater neuroprotection than other adjuvant options such as antipsychotics that reduce brain volume.  The efficacy of minocycline as a standalone antidepressant is unclear, however, patients should be evaluated on a case-by-case basis in terms of how they respond.  Someone with depression taking minocycline for another condition who reports seemingly miraculous remission of symptoms following initiation of treatment, may wish to continue with an unconventional broad-spectrum antibiotic for their depression.

Have you tried Minocycline for depression?

If you’ve tried minocycline (regardless of whether it was for depression or another condition), did you find that it improved your mood and/or other neuropsychiatric symptoms?  To help others get a better understanding of your situation, share your reason for taking minocycline, the dosage you took, as well as any other medications (or supplements) that you were using along with it.  If you had to rate its antidepressant efficacy on a scale of 1 to 10, what would you rate it?

Discuss how long you continued minocycline treatment and whether you noticed any significant unwanted side effects and/or tolerance onset over time.  Also realize that for a subset of users, minocycline could actually cause (or worsen) depression.  No intervention, especially a broad-spectrum antibiotic should be considered utopian for all users.

It is hoped that researchers continue to investigate the implications of antibiotics on mood, particularly ones like minocycline that exert noticeable effects upon the CNS. Even if minocycline is never approved by the FDA for depression, it clearly can affect mood and the brain.  Pharmaceutical developers may want to take note and consider creating an improved minocycline spinoff for the treatment, and possible prevention of depression and/or neurodegenerative diseases.

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