I was on 200mg Zoloft qd for four months back when I was in high school. I have had mood episodes resembling those of ultra-rapid-cycling bipolar II disorder since discontinuing, even seven years after the fact, which were not present before I started taking the medication.
This issue has been seriously hurting my ability to form proper social relationships, namely because I go through a depressive episode (and a hypomanic episode) once per week. During hypomanic episodes everything is fine and dandy (and I'll get into that more in a bit), but during the depressive episodes I have a low mood, low confidence and self-esteem, and in general wish to withdraw from everyone. Concentrating is much more difficult, and my mind simply reacts slower. For example, when I'm in a conversation with someone and it's my turn to respond it takes like a full three seconds for a response to fully form in my head when it used to be near-instantaneous.
From my perspective, the feeling is like my brain doesn't know how to restrain itself in expending energy used in processing responses to stimuli. During the hypomanic phases I will be very quick and agile mentally, and am able to keep up a conversation easily; "excessive" accurately characterizes the energy, the confidence, everything about this state. Then during depressive phases its the complete opposite. Its like I have no more energy to think quickly and accurately or be happy and have to wait three-ish days for the energy stores to rebuild. Unless I put every ounce of effort into restraining myself in my reactions to stimuli I cannot control these mood episodes. I can't even listen to music while running or doing cardio exercise anymore because it excites me too freaking much and will inevitably trigger an episode.
I've been through a large number of medications and supplements and nothing has worked to fix the problem (and by fix, I mean end the constant cycling). I have a dx of social anxiety disorder currently (though it is being successfully treated with CBT/exposure), and my psychiatrist no longer wants to prescribe medication for the mood swings because she thinks they are purely a product of the anxiety. At this point, I'm inclined to disagree.
I'm wondering if it was possible that my serotonergic neurotransmission has been permanently altered because of my experience with Zoloft. The only information I've been able to find on permanent changes caused by SSRIs is about post-SSRI sexual dysfunction (PSSD). Here's a summary of the available literature on the disorder.
Under the summary article, I found this study:
Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins.
Long-term exposure to fluoxetine produces a desensitization of hypothalamic postsynaptic 5-hydroxytryptamine (5-HT)1A receptors, indicated by a substantial inhibition of the 5-HT1A receptor-mediated stimulation of oxytocin and adrenocorticotropic hormone (ACTH) secretion. The present study investigated the time course and mechanism of this desensitization after discontinuation of fluoxetine administration. Male rats were injected with saline or fluoxetine (10 mg/kg/day, i.p.) for 14 days and were challenged with a 5-HT1A agonist, [8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) 50 microg/kg, s.c.] 2, 4, 7, 14, 28, or 60 days post-treatment. In control animals, 8-OH-DPAT significantly increased (approximately 15-fold) plasma levels of oxytocin and ACTH. At 2 days post-treatment, oxytocin and ACTH responses to 8-OH-DPAT were reduced by 74% and 68%, respectively. During further withdrawal from fluoxetine, there was a gradual increase in the oxytocin response toward control levels. However, even 60 days after discontinuation of fluoxetine, the oxytocin response was still significantly reduced by 26% compared with controls. In contrast, the suppressed ACTH response to 8-OH-DPAT (a less-sensitive indicator of desensitization) gradually returned to control levels by day 14 of withdrawal from fluoxetine. Interestingly, the sustained reductions in the hormone responses occurred in the absence of reductions in Gz or Gi protein levels in the hypothalamus. Furthermore, this desensitization was sustained in the absence of detectable levels of fluoxetine and norfluoxetine in plasma and brain tissue. These findings suggest that the sustained desensitization of hypothalamic 5-HT1A receptor systems, observed during fluoxetine withdrawal, may be due to altered interactions among the protein components of the 5-HT1A receptor system, rather than their absolute levels.
It seems that fluoxetine at least has the ability to effect residual changes on serotonergic neurotransmission, specifically on the 1a receptor subtype.
I've read that St. John's Wort (SJW) has been found to upregulate the 1a and 2a 5-HT receptor subtypes over the long-term, though whether this effect is persistent and residual I have not been able to clarify. The only evidence I've seen of SJW providing lasting effects are anecdotal reports of using SJW to cure PSSD, and of SJW being successfully used to rekindle the "magic" of MDMA usage. I'm wondering if the upregulation caused by SJW will be able to correct the possible dysfunctional serotonergic neurotransmission causing my mood episodes and over the long-term.
I've also looked at tianeptine and am wondering if that would help as well, since its pharmacological profile is somewhat novel regarding serotonin.
Other than those two supps I'm running out of ideas, and I'm nearly at wit's end. I don't like being medicated, but I can't go through life with these freaking mood swings anymore.
P.S. There might be a dopaminergic issue as well.
Prior to being on Zoloft I was on 60mg Adderall XR qd for 3-4 months. No mood swings were noticed then, just intense anxiety. I can't rule out the Adderall as causing the mood swings because I was put on Zoloft immediately after weaning off of the Adderall.
In this same vein, I can't tolerate vitamin D3-containing supplements. I've read that D3 upregulates expression of tyrosine hydroxylase, which is the rate-limiting enzyme in the conversion pathway for dopamine. Taking even as low as 800 IU a day for a couple of weeks prolongs the hypomanic phase by two days or so, but GREATLY increases the cognitive deficits associated with the depressive phase to the point where my concentration and focus are absolute shit, my short-term memory is incredibly short, and my ability to plan tasks i.e. for helping a patient with an issue in the pharmacy, is shot.
Edited by Professorben11, 21 January 2015 - 03:06 AM.
