SSRIs

SSRIs
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Formula	N/A
Administration	Oral
Solubility
Legal status	Rx
Brand names	Zoloft, Lexapro, Prozac, Celexa, Paxil, Luvox
Bioavailability
Recommended dose	Don't
Upper limit	Anything above 1 pg
LD50	Looking at them
Ray's verdict	Hell

“Uncontrolled serotonin is a major factor in destructive, seemingly uncontrolled aggression…. inclinations of the same sort when combined with social and economic power… become potentially world destroying” - Ray Peat

Introduction

Selective Serotonin Reuptake Inhibitors (SSRIs) are a class of drugs commonly prescribed as antidepressants and anxiolytics. While mainstream psychiatry often views depression as the result of a "chemical imbalance" (specifically a lack of serotonin, frequently mischaracterized as the "happy hormone"), the bioenergetic perspective offers a diametrically opposed view.

According to Ray Peat, serotonin is a hormone of stress, hibernation, and metabolic suppression. In this framework, SSRIs, by increasing serotonin concentration in the synaptic cleft, do not correct a deficiency. Instead, they can exacerbate metabolic stress, reduce cellular energy production (mitochondrial respiration), and act synergistically with estrogen and prolactin.

More in Serotonin

Structure / Chemical properties

Unlike some other drug classes, SSRIs do not share a uniform chemical structure. They are primarily defined by their pharmacological activity: their ability to bind to the serotonin transporter (SERT) and inhibit its action.

However, it is notable that many of them contain halogen atoms (such as fluorine in fluoxetine or chlorine in sertraline).

From a bioenergetic standpoint, this can contribute to their toxicity and their interference with thyroid function, as halogens can compete with iodine and disrupt thyroid hormone synthesis.

Function / Mechanism of action

SSRIs block the serotonin transporter (SERT) at the presynaptic membrane. This prevents the reuptake of released serotonin, thereby increasing its concentration and the duration of its action in the synaptic cleft.

Medical uses / Effects

"Because it hasn’t been possible to provide evidence to support the idea that serotonin is a mood elevator happy hormone, the industry has looked for some way to explain the therapeutic benefit that they claim. They have generally settled on the idea that the SSRIs, after several weeks of use, increase the synthesis of the progesterone metabolite allopregnanolone, in the brain. That does happen, but the synthesis of those defensive steroids is also increased by any injury to the brain" - Ray Peat

Since the serotonin hypotesis, chemical inbaalance and it's genetic basis is faulty, SSRIs don't really help, they numb, the only benefit is the increase in allopregnenalone as a defense mechanism of the brain. This treatment is ineffective as proven by the Meyer study found no relationship between how much the striatal occupancy and how much the patients actually felt better shown on the Hamilton scale.

Research shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.

Autopsy of suicide victims show high serotonin levels.

Side / Adverse effects

https://x.com/pikeypilled/status/1884237602859147283

Some are unknown to the public, because of deliberete withholding of information by the doctors, black-box warnings and hiding clinical data from the public

• Inability to feel love: Selective serotonin reuptake inhibitors were found to reduce the intensity and duration of feelings of love
• Loss of desire/libido:
  • In a Spanish study of 1022 patients
    • 57% experienced decreased libido
    • 57% experienced delayed orgasm or ejaculation
    • 46% experienced no orgasm or ejaculation
    • 31% experienced erectile dysfunction or decreased vaginal lubrication.
• Learned helplessness: No drive to exit a toxic situation
• Emotional numbness: Anhedonia, decreased empathy
• Depersonalization
• Cognitive decline: Faster cognitive decline, 35% increased risk of severe dementia, earlier death for dementia patients
  • Symptoms also include: confusion, distorted thinking, convulsions, amnesia, brain-zaps
• Bone density loss: 25% increased fracture risk
• All-cause mortality. 18% increase
• Bipolar disorder: Significantly raises the risk
  • Studies:
    • SSRIs associated with a 7.7% annual rate of new bipolar diagnoses (tripling the baseline rate).
    • 60% had their first manic episode after starting antidepressants for depression.
    • 1 of 184 hospitalized patients on SSRIs developed mania and 8 became psychotic
      • 8% of 533 Yale admissions were for antidepressant-caused mania/psychosis.
• Violence:
  • A 2020 Swedish register-based study found that SSRI use is associated with an increased risk of violent crime convictions persisting during treatment and up to 12 weeks after discontinuation,
    • Raised serotonin itself even without supplementation is proven to increase violent tendencies
• Suicide:
  • In a trial, SSRIs doubled the risk of harms related to suicidality and violence in adult healthy volunteers with no mental disorder.
  • Study of 20 mentally healthy volunteers reported that Zoloft made 2 become suicidal, one close to actually comitting suicide, both of whom remained deeply disturbed for months.
• Antidepressant Withdrawal Syndrome

New Zealand survey on 1,829 patiensts: 62% reported sexual difficulties, 60% felt emotionally numb, 52% felt not like themselves, 39% cared less about others, 47% had experienced agitation and 39% had experienced suicidal ideation.

Other adverse effects

Insomnia, nightmares, ‘Fuzzy’/‘zombie,’ jaw grinding, sweating, blurred vision, constipation, disturbed/restless sleep, anxiety, heart palpitations, difficulty thinking, fatigue/exhaustion, strange/vivid dreams, stiff muscles/joints,’ mania, excessive yawning, panic attacks, memory loss, decreased motivation, night sweats, decreased appetite, feeling agitated, shaky or anxious, indigestion, stomach aches and diarrhea.

Pregnancy adverse effects

shorter babies with smaller heads in mothers taking them during pregnancy

30% of babies will also experience “neonatal adaptation syndrome” (withdrawals) post birth

Tapering off

"It takes time to adapt to decreasing those drugs, keeping sugar up and inflammation down, including bag breathing, should help. Starting with a little, a sixth or fourth of a tablet, of cynoplus in the evening would be the best way to try it." - Ray Peat

Getting the tapering off right is vital, having high metabolism and the right hormonal ballance lessens the "fall".

Keeping the metabolic rate and cholesterol up is important, so that repair and adaptation will be quick. Progesterone reduces pain and anxiety, and pregnenolone would be the most convenient supplement for men, but it's hard to find products without allergens. Combining progesterone and DHEA or testosterone can produce the stabilizing effect without suppressing the libido. Benadryl and cyproheptadine are probably both helpful. Withdrawal from morphine and SSRIs and migraine involve some similar processes.

It depends on how much pregnenolone you can assimilate. People would use progesterone in amounts needed to stop the withdrawal symptoms, but pregnenolone doesn't have the powerful effects of progesterone, even in multi-gram quantities, so it's just a matter of seeing what it can do. As I understand the mechanism (migraine, withdrawal, etc.), estrogen-histamine-serotonin rise on a background of hypothyroid liver malfunction, cytomel (and/or sugar, selenium, B vitamins) allows the liver and other detoxifying systems to lower them, and the lower they are, the less progesterone or pregnenolone it takes to block the symptoms.

Linear Tapering

• Fixed dose reductions (e.g., 50% every 2-4 weeks) down to minimum therapeutic dose
• Simple, guideline-recommended, but can cause intense withdrawal symptoms (up to 78% in short tapers) due to abrupt SERT occupancy drops
  • Often leads to relapse misdiagnosis; success variable.

Hyperbolic tapering

• Method for discontinuing SSRIs, proposed by Dr. Mark Horowitz in 2019.
• Larger initial dose reductions followed by progressively smaller reductions to minimize withdrawal symptoms, contrasting with traditional linear tapering.

Rationale

Based on the hyperbolic relationship between SSRI dosage and serotonin transporter (SERT) occupancy. Even small doses maintain significant SERT occupancy, necessitating gradual reductions at lower doses to avoid abrupt drops that trigger severe withdrawal effects.

Comparison with linear tapering

Linear tapering reduces doses by fixed amounts, which can lead to intense withdrawal symptoms at lower doses. Hyperbolic tapering mitigates this by aligning dose reductions with the drug's pharmacodynamic effects, resulting in milder and more manageable symptoms.

Implementation

The method recommends starting with larger reductions and slowing down as doses decrease, potentially extending over six to twelve months or longer. Options include using liquid formulations, compounding pharmacies, pill-cutting, or bead-counting for precise dosing. Specific schedules, such as reducing escitalopram from 10mg to 0mg in steps like 5mg, 3mg, 1.5mg, 1mg, 0.5mg, and 0.25mg, are highlighted as effective.

Managing withdrawal symptoms

Supportive measures are emphasized, including high-dose magnesium, thiamine (with caution on forms like TTFD initially), taurine, glycine, and L-theanine to balance GABA/glutamate and reduce excitotoxicity. Sodium supplementation is advised to counter hyponatremia, potentially using skimmed milk with salt. Avoiding additional serotonin-modulating agents during tapering is recommended to clearly identify withdrawal effects.

Potential challenges and considerations

Prolonged tapering might sometimes exacerbate symptoms in certain cases, leading to protracted withdrawal. A study advises monitoring for misinterpretation of withdrawal as relapse and suggests short term fluoxetine substitution for high-risk SSRIs, though fluoxetine is not self-tapering despite its long half-life.

Outcomes and evidence

Observational data indicates hyperbolic tapering is associated with limited, rate-dependent withdrawal symptoms, with success rates around 72% in case studies. It stresses the importance of personalized schedules and professional guidance to achieve antidepressant-free status without significant issues.

Brands and sources

Brands

• Zoloft (sertraline)
• Lexapro (escitalopram)
• Prozac (fluoxetine)
• Celexa (citalopram),
• Paxil (paroxetine),
• Luvox (fluvoxamine)

Sources

Doctor who hates you.