The Brain is Always Seeking Homeostasis
It’s unsettling when your neurophysiology feels off-kilter.
You start to wonder, “when will I feel myself again?” The answer is: you will feel better, it just takes time for your brain to re-equilibrate.
Your brain is self-regulating and always seeking a homeostatic setpoint.
Benzobuddies is a whole community built around coping with benzodiazepine withdrawal. Benzodiazepine withdrawal is worst flavor of drug withdrawal because it can be so long-lasting.
SSRI withdrawal pales in comparison to benzodiazepine withdrawal – but it’s still nothing to sneeze at.
Lexapro Withdrawal or Depression?
Getting back to Lexapro: be mindful of the difference between Lexapro withdrawal and a resurgence of depressive symptoms.
If you’ve discontinued Lexapro and experience worsening depressive symptoms – that’s not a good sign. There are a few studies that discuss the “chronification” of depression via antidepressants.
The idea is that antidepressant therapy followed by withdrawal can worsen the course of depression. The brain adapts to a “hyperserotonergic” state, which could theoretically prime it for depression after discontinuation.
This thesis is developed in Rif S. El-Mallakh’s paper, which the author calls tardive dysphoria. Here’s a quick excerpt from the abstract 1.
Treatment-resistant and chronic depression appear to be increasing. The recent identification of antidepressant tachyphylaxis, the loss of antidepressant efficacy over time, is only a partial explanation. This is an emerging evidence that, in some individuals, persistent use of antidepressants may be prodepressant.
Background Info on Lexapro
Lexapro (Escitalopram) is one of the most popular antidepressant drugs in the United States 2.
It is a selective serotonin reuptake inhibitor (SSRI) that is also closely related to the SSRI citalopram (Celexa).
Chemically, citalopram contains 50% Lexapro (escitalopram) because it’s racemic. Escitalopram is one mirror image of the 50/50 racemic mixture in citalopram (Celexa). Lexapro can be crudely conceptualized as a more purified form of Celexa (citalopram) 3.
SSRIs are widely used in the treatment of depressive and anxiety disorders. But they’re not necessarily more effective than the old-school tricyclics antidepressants. In fact, SSRIs are probably less effective than tricyclics. Their surge in popularity is due to their favorable side effect profile, safety in overdose, and overall tolerability 4.
SSRIs are associated with recognizable withdrawal symptoms, called the SSRI discontinuation syndrome [^4].
How Lexapro Works
Patients prescribed Lexapro typically take one 10mg tablet a day. But Lexapro is also available in 5 mg and 20 mg doses.
SSRIs in general (Lexapro included) increases the amount of serotonin between synapses. (In case you’re unfamiliar: synpases are connections that allow neurons to communicate).
Serotonin is a neurotransmitter — a chemical that relays signals between the cells in your brain. Serotonin affects mood and social behavior, appetite and digestion, sleep, memory, and sexual desire [^5].
The Monoamine Hypothesis
For many years it was thought that depression is a “serotonin deficiency syndrome.” Researchers called this the “monoamine hypothesis.” Neuroscientists now consider this view to be overly simplistic.
While it’s true that boosting monoamines (serotonin, dopamine, norepinephrine) positively affects mood, relief from depression is much more complicated. The brain is finely tuned and intricate – not a bag of chemicals.
Lexapro increase serotonin, which does ultimately reduce the symptoms of depression and anxiety. But serotonin only indirectly affects mood by increasing the rate of neurogenesis (among other things) [^6].
Besides serotonin, SSRIs also modulate other systems in the brain like noradrenaline and dopamine.
Lexapro Takes Time to Work
After starting to take Lexapro and taking it every day, symptoms usually begin to improve during the first 1–2 weeks, and maximal improvement is usually seen after 4–6 weeks [^7].
Researchers have puzzled over this lag time because the effect of escitalopram (Lexapro) on serotonin is near-instantaneous. Different ideas have been developed to explain the therapeutic lag, such as receptor downregulation and neurogenesis.
Therefore, Lexapro typically requires being taken for a continued period of time for it to become effective as a treatment.
Lexapro Withdrawal Symptoms
Lexapro and SSRIs generally, are associated with well-recognized withdrawal symptoms. The withdrawal symptoms occur within a few days of a patient stopping the medication, and last for a few weeks.
Case reports of Lexapro have revealed that patients experienced electric-shock sensations up to 4 weeks after they stopped taking the drug [^8]. These are colloquially referred to as the “zaps.” Yet, many variations are possible, including symptoms appearing later or persisting for longer.
There are a wide range of withdrawal symptoms associated with Lexapro 5, which can be divided into subcategories. These are listed below:
- Affective Symptoms: Anxiety, Agitation, Nervousness, Low mood, Irritability
- Sensory Symptoms: Paresthesia (typically tingling or pricking, “pins and needles”), Electric shock-like sensations (“Brain zaps”)
- General Somatic Symptoms: Headache, Tremor, Lethargy, Sweating
- Disequilibrium: Light-headedness, Dizziness, Vertigo or Feeling faint
- Sleep Disturbances: Insomnia, Nightmares
- Gastrointestinal (GI) Symptoms: Nausea, Emesis (the act or process of vomiting), Diarrhea
Not all patients treated with Lexapro experience these withdrawal symptoms. There’s lots of heterogenity in how withdrawal symptoms manifest.
Here’s an example. In patients with social anxiety disorder, rates of symptoms after treatment ranged from 17 to 27%. Other, more general, symptoms may occur when patients stop taking antidepressant medication.
These nonspecific discontinuation symptoms include 6:
- appetite changes
- libido changes
- mood swings
- suicidal thoughts
- weight changes
What Factors Influence Lexapro Withdrawal?
The withdrawal symptoms you’d expect to encounter after stopping Lexapro depend on many factors.
Alas, there is no exact timeline for determining how long it will take you to return to your familiar self.
But remember that withdrawal symptoms can persist for longer than expected. Take these factors into consideration:
The single most important takeaway is that you should taper when discontinuing SSRIs.
Gradually taper down the dose of medication rather than abruptly ending treatment. This gives your brain time to adjust to a knew neurochemical milieu (environment).
Expectedly, tapering is likely to decrease both the severity and duration of withdrawal symptoms.
In patients taking Lexapro, the incidence of symptoms during tapered withdrawal was low (e.g. 2-12%). So even if you taper gradually, you may still experience withdrawal symptoms 7. But they’ll be diminished in severity and much more manageable.
The recommended dosage of Lexapro is to take one 10mg tablet a day. However, this can be increased up to 20mg if required. Inevitably, the larger the dosage, the stronger the withdrawal symptoms will be, and therefore the longer it will take to taper off the treatment and for withdrawal symptoms to stop.
SSRIs with a shorter half-life tend to cause more frequent withdrawal symptoms 8.
If you’re unfamiliar, the half-life is the amount of time it takes for 50% of the drug to be eliminated from your bloodstream.
It makes intuitive sense that SSRI half-life is associated with the severity of discontinuation symptoms. If the half-life is really long, then after you stop the drug, levels will decline slowly.
When taken into consideration, Lexapro has a reasonably long half-life of 30 hours, compared to other SSRIs. Here’s a table comparing half-lives 9:
- Paroxetine: 24 hours
- Fluvoxamine: 15 hours
- Citalopram: 33 hours
- Escitalopram: 30 hours
Length of Treatment
To date, there is no evidence to suggest that the length of SSRI treatment is associated with the development of more withdrawal symptoms, or with the severity of those symptoms.
Prior to antidepressant therapy, patients and caregivers need to be well informed about the possible outcomes during and following treatment. All to frequently, physicians gloss over antidepressant withdrawal symptoms. This isn’t entirely their fault, since SSRI discontinuation symptoms were only recognized recently.
Don’t forget to expect individual variation in withdrawal symptoms. This heterogeneity is related to genetic variability and countless other factors 10.
How Effective Is Lexapro Compared with Other SSRIs?
A few studies have compared Lexapro with the other SSRIs 11.
Patients taking Lexapro reported reduced withdrawal symptoms compared to venlafaxine XR (Effexor) and paroxetine (Paxil).
In patients with combined social anxiety disorder and generalized anxiety disorder the same pattern emerged. Compared with paroxetine, Lexapro discontinuation was less severe 12.
Patients taking Lexapro reported lower withdrawal symptoms than those taking paroxetine 13.
Understanding the Withdrawal Symptoms
When drug treatment ends, the brain will continue to function in a similar way, despite the reduction in available serotonin – resulting in the occurrence of withdrawal symptoms.
Yet, the mechanisms involved in the brain and body that cause these withdrawal symptoms are still not very well understood. A number of mechanisms have been suggested:
- A behavioral stress response that is associated with increased deep brain activity
- Genetic vulnerabilities
- Receptors in the brain are used to functioning at a less active level, which has a downstream effect on other neurotransmitter systems
Further research will shed light on the causes of the withdrawal symptoms associated with Lexapro.
- El-mallakh RS, Gao Y, Jeannie roberts R. Tardive dysphoria: the role of long term antidepressant use in-inducing chronic depression. Med Hypotheses. 2011;76(6):769-73. ↩
- Lockhart P, Guthrie B. Trends in primary care antidepressant prescribing 1995-2007: a longitudinal population database analysis. Br J Gen Pract. 2011;61(590):e565-72. ↩
- Bezchlibnyk-butler K, Aleksic I, Kennedy SH. Citalopram–a review of pharmacological and clinical effects. J Psychiatry Neurosci. 2000;25(3):241-54. ↩
- Dunlop BW, Davis PG. Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review. Prim Care Companion J Clin Psychiatry. 2008;10(3):222-8. ↩
- Pearlstein T. Perinatal depression: treatment options and dilemmas. J Psychiatry Neurosci. 2008;33(4):302-18. ↩
- Targum SD. Identification and treatment of antidepressant tachyphylaxis. Innov Clin Neurosci. 2014;11(3-4):24-8. ↩
- Marcinkiewcz CA, Lowery-gionta EG, Kash TL. Serotonin’s Complex Role in Alcoholism: Implications for Treatment and Future Research. Alcohol Clin Exp Res. 2016; ↩
- Marken PA, Munro JS. Selecting a Selective Serotonin Reuptake Inhibitor: Clinically Important Distinguishing Features. Prim Care Companion J Clin Psychiatry. 2000;2(6):205-210. ↩
- Fiedorowicz JG, Swartz KL. The role of monoamine oxidase inhibitors in current psychiatric practice. J Psychiatr Pract. 2004;10(4):239-48. ↩
- Brigitta B. Pathophysiology of depression and mechanisms of treatment. Dialogues Clin Neurosci. 2002;4(1):7-20. ↩
- Kennedy SH, Andersen HF, Lam RW. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci. 2006;31(2):122-31. ↩
- Preventing recurrent depression: long-term treatment for major depressive disorder. Prim Care Companion J Clin Psychiatry. 2007;9(3):214-23. ↩
- Rustad JK, Stern TA, Hebert KA, Musselman DL. Diagnosis and treatment of depression in patients with congestive heart failure: a review of the literature. Prim Care Companion CNS Disord. 2013;15(4) ↩