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PostPosted: Tue Jan 31, 2012 2:47 am 
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I'm certain this has been the case in me. Some background?

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Antidepressant Apathy Syndrome

December 18, 2005

By Lee, Stacey I; Keltner, Norman L

“You know I used to become unglued whenever the neighborhood kids would ride their bikes through my lawn. Since I’ve been taking Prozac I just don’t give a shit. Tell the little bastards to come on. I tell you, Prozac is great.”

65-year-old neighbor in 2003

This paper will explore the phenomenon of antidepressant apathy syndrome (AAS). Included in this discussion will be efforts to (i) differentiate depression and apathy, (ii) explore relevant case reports, (iii) look at the relationship between apathy and violent behaviors in adolescents, (iv) discuss apathy as a desired effect, (v) suggest possible mechanisms causing AAS, and (vi) explore treatment strategies.

Introduction

Selective serotonin reuptake inhibitors (SSRIs) have been reported to induce an amotivational or apathy syndrome in both children and adults being treated for panic disorder, obsessive- compulsive disorder (OCD), and depression (Garland & Baerg, 2001; Hoehn-Saric, Lipsey, & McLeod, 1990; Hoehn-Saric, Harris, Pearlson, Cox, Machlin & Camargo, 1991). The presentation of apathy in the absence of depression associated with long-term SSRI therapy has been referred to as antidepressant apathy syndrome (AAS) and proposed as a unique syndrome distinct from depression (Marangell, Johnson, Kertz, Zboyan, & Martinez, 2002). Antidepressant apathy syndrome is considered a late-occurring event, dose related, and reversible (Hoehn-Saric et al., 1990, 1991). Despite detrimental social and financial consequences, AAS often goes unreported and undetected (Barnhart, Makela, & Latocha, 2004). Recognition of this phenomenon is the first critical step toward intervention.

Depression or Apathy?

Apathy, from the Greek word pathos for passion, literally means a lack of passion for life. Apathy is defined as a syndrome in which there are lack of motivation, indifference, disinhibition, and poor attention not attributable to cognitive impairment, emotional distress, or diminished level of consciousness (Marin, 1990). Depression involves emotional distress, sadness, anxiety, agitation, and feelings of worthlessness and hopelessness (American Psychiatric Association, 2000). Other common symptoms experienced in depression are physical inactivity, social inactivity, and diminished interest (Table 1). These latter symptoms overlap with apathy and cause diagnostic confusion (Levy et al., 1998). Marin (1990) points out a key diagnostic point: although externally inactive, depressed patients may be in great internal emotional distress. Levy et al. (1998) also suggest that much of the overlap between apathy and depression is compounded by the use of depression scales containing apathy items.

Levy et al. (1998) and Marin (1990) have made great strides to distinguish depression and apathy as two unique disorders. There is increasing evidence suggesting that apathy may also be a late- occurring complication of SSRI treatment separate from the original diagnosis (Garland & Baerg, 2001; Hoehn-Saric, et al., 1990,1991). Hoehn-Saric et al. (1990) initially reported SSRI-induced apathy in a case report of patients with depression and anxiety disorder. More recently, Garland and Baerg (2001) reported five cases of AAS among young people. It is important to note that before clinicians were aware that SSRIs could potentially induce apathy, it was rarely reported (Walkup & Labellarte, 2001). Furthermore, patients fighting anxiety or depression may ignore the insidious onset of apathy until most of their original symptoms are gone. At this late stage in treatment, apathy may be misdiagnosed as a relapse of the primary condition or considered treatment “poop out” (i.e., loss of efficacy). Distinguishing AAS from relapse and “poop out” has clinical implications regarding treatment and management strategies (Barnhart et al., 2004; Marangell et al., 2002).

Case Reports

Hoehn-Saric etal. (1990) reported five patients receiving fluvoxamine or fluoxetine who developed lack of motivation, indifference, disinhibition, and poor attention without concurrent sedation. The cases included two patients with panic disorder prescribed fluvoxamine, and three patients with major depression taking fluoxetine. The manifestation of apathy appeared to be dose related and reversible, depending on the drug’s half-life.

Case 1

A 55-year-old male engineer began fluvoxamine titrated to 300 mg/ day for panic disorder. At this dose, he experienced the side effects of increased perspiration, tiredness, and difficulty maintaining an erection. His dose was decreased to 150 mg/day, which was sufficient to control his panic attacks. However, the patient reported becoming indifferent towards the fulfillment of his duties. He stopped paying his utility bills for 3 months and was consistently late for work. Gradually, the patient realized the extent of his neglect but failed to get upset about it. Fluvoxamine was decreased to 100 mg/day. The feeling of apathy dissipated, and he returned to his normal work habits.

Case 2

A 35-year-old female executive developed panic attacks at the age of 30, which later evolved into agoraphobia. She was eventually placed on fluvoxamine and titrated to a dose of 400 mg/day over a 3- month period. At this dose she became free of panic attacks but began to experience apathy, indifference, and disinhibition. She reported neglecting her children and losing interest in her work. Although in a stimulating environment, she became disinhibited and impulsive. Her medication was reduced to 150 mg/day and her condition normalized in 3 days.

Case 3

A 39-year-old female graduate student presented with symptoms of major depression. She was placed on fluoxetine 20 mg every other day for 4 days, followed by 20 mg/day. Within 8 weeks her initial depressive symptoms resolved, but she complained of a new sense of apathy regarding her professional career. She stated this feeling was completely different from a sense of sedation and was unlike the lack of motivation she had experienced during her depression. As a result of these new symptoms, she was switched to the monoamine oxidase inhibitor, tranylcypromine.

Case 4

A 37-year-old female psychotherapist was seen for symptoms of chronic major depression. She was given a trial of fluoxetine 20 mg/ day. After 6 weeks of treatment she was euthymic. At 6 months she reported a slowly growing sense of lack of motivation and apathy. She reported talking with friends less often, not paying bills on time, and found it difficult to care about anything. She also stated that these feelings bore no relationship to depression. She was switched to amitriptyline, preferring to be sedated over being apathetic and unmotivated.

Case 5

A 50-year-old female illustrator was seen for recurrent major depressive episodes. She was started on fluoxetine 20 mg/day and later decreased to 20 mg every other day because of nausea. Five weeks into treatment she complained of a sense of apathy and a lack of motivation. She felt this was unlike prior side effects or previous symptoms of depression. The dose of fluoxetine was increased to 20 mg/day then eventually to 40 mg/day. The patient’s symptoms of depression were fully resolved, but she continued to complain of apathy, especially with respect to her work. She stated “this is what a frontal lobotomy must be like” (p. 345). Her fluoxetine was slowly tapered down with a partial improvement in her apathy.

These cases presented by Hoehn-Saric et al. (1990) are all similar in that the apathetic symptoms developed gradually, were not associated with sedation, and were not identified as abnormal until they caused social and financial repercussions.

Garland and Baerg (2001) reported similar symptoms of apathy in children and adolescents treated with paroxetine and fluoxetine for depression, anxiety, and obsessive-compulsive disorder. Symptoms were late in onset, dose related, and reversible. The five cases illustrate the detrimental impact AAS can have on development related to schoolwork, social relationships, and sports involvement. In all cases, the patients were unaware of their apathetic state and reported feeling “fine” despite their parent’s concerns. In four out of the five cases, management consisted of dose reduction. In the fifth case, bupropion was added in addition to reducing the SSRI dose.

Are Adolescent Violent Behaviors Related to Apathy?

Suicide

February 2004: Kara Jayne-Anne Otter, 12, taking Paxil for depression, killed herself. Her mother, Shannon Baker, blames the SSRI. Time, February 9, 2004 (Lemonick, 2004).

Murder and Suicide

March 2005: Jeff Weise, 16 years old, opened fire on faculty and students at Red Lake High School, killing nine. His family wondered if his medication (Prozac) might have contributed to his loss of control. Minneapolis Star Tribune, March 23, 2005 (Meryhew, Haga, Padilla, & Oakes, 2005).

Table 1. Differentiating Apathy and Depression

Murder

February 2005: A 15-year-old boy in Charleston, SC killed his grandparents. He claimed the antidepressant Zoloft drove him to it. Birmingham News, February 16, 2005 (Smith, 2005).

Antidepressants are known to increase suicide risk. Traditionally, this upswing in suicidal behaviors was explained away as an increase in psychic energy created by the very tools being used to treat depression-antidepressants. In other words, it was thought that anti\depressants, early on in treatment, posed a risk of giving “legs” to ideations formerly devoid of energy. However, a spike in energy does not convincingly explain the kind of SSRI- linked behaviors that have made headlines in recent years. While this conclusion is not novel, not many are suggesting that the apathy caused by SSRIs may prove to be a viable explanation. The powerful examples noted previously and numerous others drove the FDA to issue black box warnings on antidepressants related to their potential to cause these behaviors in young people.

Apathy as a Desired Effect

As suggested in the opening scenario, a number of anecdotal reports indicate some people appreciate the apathy associated with SSRIs. The 65-year-old neighbor practically rejoices in not caring anymore about what the neighborhood kids do to his yard. At first glance, this might appear to be growth in the Eriksonian sense, but is it? An equally viable explanation is SSRI-induced indifference. Another example is the older man in an unhappy marriage, who confided to the authors that he likes “not hurting” anymore. He also offers the added benefit of a decreased sex drive with the SSRI he is prescribed because “My sex life is nonexistent but I don’t believe in divorce.”

These and other clinical reports suggest that, for some individuals at least, SSRIs provide a way of avoiding their problems. Although not an approach clinicians can comfortably endorse, this is actually the biggest plus for some patients.

Possible Mechanisms of AAS

SSRIs increase serotonin in the brain and serotonin is primarily an inhibitory neurotransmitter. Of course, the person experiencing apathy looks very inhibited. Emotions, motivation, interest, and normal inhibition are inhibited, causing disinhibition. Serotonergic extensions projecting from the raphe nuclei of the brainstem pervasively connect to cortical neurons, including those in the frontal lobe. According to Cowen (1991), each serotonergic neuron makes 500,000 synaptic connections in the cortex or limbic areas. How this revving up of the serotonin system may contribute to apathy is not clear; however, Barnhart et al., (2004), Hoehn-Saric et al. (1990, 1991), Levy, et al. (1998), and Marangell et al. (2002) suggest two possible explanations for AAS.

Direct Effect

Serotonin directly affects frontal lobe projections that modulate initiative, curiosity, inhibition, and ability to focus. According to this view, as serotonin receptors are bombarded with increasing amounts of serotonin, these frontal lobe functions devolve into lack of motivation, disinterest, disinhibition, and poor attention.

Indirect Effect

SSRIs indirectly modulate frontal lobe activity by inhibiting the release of dopamine. It is this knowledge (i.e., serotonin inhibits dopamine) that has led to the development of atypical antipsychotic drugs. Because negative and cognitive symptoms of schizophrenia are thought to be related to hypodopaminergia in the mesocortical tract by blocking serotonergic influence on dopamine neurons, these symptoms can be treated. All atypical antipsychotics work by inhibiting a particular serotonin receptor, 5HT^sub 2A^. Hence, according to the second explanation, by increasing serotonin in the frontal cortex, SSRIs are diminishing dopamine there and causing apathy. It must be noted as well that apathy is considered a negative symptom of schizophrenia.

Treatment Strategies

As stated earlier, distinguishing SSRI-induced apathy from “poop- out” or relapse has clinical implications regarding treatment and management protocols (Barnhart et al., 2004; Marangell et al., 2002). Once AAS has been identified, there are three primary treatment strategies: (i) decrease SSRI dose until apathy subsides, (ii) augment SSRI with a stimulant or with an antidepressant with noradrenergic or dopaminergic activity, and (iii) switch to a different class of antidepressants (Barnhart et al., 2004; Garland & Baerg, 2001; Walkup & Labellarte, 2001). If it is impossible to decrease the SSRI dose low enough to resolve the apathy while maintaining anxiety or depression control, then adding a stimulant, norepinephrine enhancing antidepressant (e.g., secondary amine TCA), or dopamine enhancing antidepressant (e.g., bupropion) may prove beneficial. Should that approach fail, strategy iii may be necessary (Barnhart et al., 2004; Walkup & Labellarte, 2001). It is important to note that AAS has been observed with all SSRIs but not with monoamine oxidase inhibitors or tricyclic antidepressants (Garland & Baerg, 2001; Hoehn-Saric et al., 1990).

What if a differential diagnosis cannot be made? In this situation it is recommended to first increase the dose, knowing fully well that apathy is likely to increase at a higher dose (Walkup & Labellarte, 2001). This is the most logical choice because lack of motivation, indifference, disinhibition, and poor attention will worsen if it is apathy. At that time, the dose can safely be decreased until apathy dissipates. Conversely, if AAS is incorrectly assumed, initially lowering the dose puts the patient at risk for relapse. This strategy is only recommended when a differential diagnosis cannot be made based on clinical signs and symptoms.

Recently, a trial was conducted to determine if adding olanzapine to ongoing SSRI treatment would abate the symptoms of AAS (Marangell et al., 2002). The rationale for this study was based on the observation that apathy associated with frontal lobe injury responds to medications that increase dopamine in the mesocortical tracts. Olanzapine has been shown to enhance dopamine in the frontal cortex by blocking serotonin-induced inhibition of dopamine release. Also, AAS shows some resemblance to the negative symptoms of schizophrenia, which readily responds to atypical antipsychotic medications like olanzapine. This research demonstrated significant improvement in apathy, therefore offering another possible treatment strategy (Marangell et al., 2002).

Conclusion

AAS is becoming a common occurrence in treatment with SSRIs. At times, AAS cannot be distinguished from depression, thus confounding treatment. At other times, AAS may be welcomed by patients because they can hide from pain and misery inside the apathy. And, at still other times, some violence linked to SSRJs may well turn out to be a variant of apathy-”nothing matters-why not!” Nurses are encouraged to assess for signs of AAS and to help the patient make good decisions when it is recognized.


I talked about this a lot in another thread I wrote, so I won't go into too much detail about my own experiences. Except to say the only times I've relapsed in the last 3-4 years has been shortly after going back on anti-depressants. I was made to doubt this possibility by my doctor for a long time, up until recently.

It's been shown that, for a lot of people, SSRI antidepressants can decrease inhibitions, increase impulsivity and apathy. At least for me, I need strong inhibitions to prevent use, and LESS impulsivity and less apathy. So by going on anti-depressants, often I lose all the qualities that I've been working on to keep myself clean.

I relapsed at 13 months clean three days after being put on Effexor. I remember not caring at all about the fact I'd lose my housing (I was in a support house), and I'd be homeless in a city 1800kms away from all family. As I was driven to the ghetto with the sickest girl in NA, knowing the drama it would cause... I just didn't care. Despite every day for the last year obsessively working on my recovery. All year I focused on the consequences of my using. Within 1-2 days of going on that medication, I just didn't care. It was frightening.

The antidepressant apathy syndrome is also called Frontal Lobe Syndrome, because SSRI's have been shown to inhibit the circuits in the frontal lobe related to impulse control and inhibition. Interestingly enough, these are the same circuits my doctor says need to be reinforced in addiction recovery.

I cannot find any resource anywhere that makes the link between addiction relapse and SSRI treatment, but the description of Frontal Lobe Syndrome is a big indicator that there's a possible link for some people. Especially those who use less when they're depressed, and more when they're impulsive or apathetic.


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PostPosted: Tue Jan 31, 2012 10:54 am 
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Hey T,

That's a fascinating article and particularly relevant to addicts because it seems most of us addicts have some kind of underlying "mental thing" going on. It's my understanding that many addicts, once clean, end up going on some kind of anti-depressant. After reading this article, it's apparent how dang careful we have to be that we're not actually making things worse for ourselves.

I know I tried Celexa there for a few days to help with my OCD, that Celexa made shit 10 times worse for me. I then switched to Wellbutrin and it seemed to work fine, but I quit taking it after only a couple of weeks. It's like I just needed that temporary "push" in the right direction from the Wellbutrin to get my footing back under me?

I noticed in the article that the first couple of cases reported that their apathy diminished greatly with a dose reduction, is this something you could try? Or, like I mentioned, would getting on an AD short term be enough to get you pointed in the right direction again? I know you mentioned how you relapsed after being on an AD for only a short time, maybe a lower dose and short term use would work?? Ah hell, I don't know?? I'm just throwing crap against the wall to see if anything sticks.

Anyway, fascinating article, thanks for posting it.

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Be kind to yourself. Our character defects do NOT define who we are!


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PostPosted: Tue Jan 31, 2012 7:38 pm 
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My doctor came up with the same idea Romeo re dose reduction. For me at least, a dose of anti-depressants either works completely or it doesn't work at all. ie there's no middle ground, no "mild" anti-depressant dose. ie I may start off on 30mg and it works, then 2 weeks later I start swinging into depression again, it happens more and more until the depression is there 24/7. So the dose gets increased, and it works again, but the same thing happens a few weeks later.

It seems at least for me, as long as an anti-dep is working, I get the apathy effect.

I understand that for many people, this may not be the case with anti-depressants. Especially for people who used to try and self-medicate their depression with opioids. But I stopped using heroin for depression a long time ago. Heroin just 'stopped working' in that aspect. If anything it just made me feel worse, and guilty for doing it. When I'm depressed, I'm conscious of the negative consequences of using - ie "But using's fucked it'll just make me feel worse"... (of course I feel the same about everything else, but at least it stops me using)... It seems to be when I'm happy and disinhibited and impulsive that I desire drugs these days, as I'm oblivious to the consequences.


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PostPosted: Tue Jan 31, 2012 8:47 pm 
HI tj
That’s interesting what you said about anti-depressants.
About 5 years ago, after a Long period of sobriety I went on Lexapro, it just so happens to coincide with four and a half years of crazy fucked up behaviour. On top of drinking like a camel I started taking OTC codeine meds to the point where I was hospitalised twice for paracetamol poisoning, then I started playing Russian roulette with Cold Water Extraction and then after having a routine X-Ray It was discovered that I had two crushed vertebrae (wedge fractures) WooHoo, I milked that for all that it was worth, managed to find a “good” Doctor who put me on Endone (at my suggestion) and then OxyContin. Within 12 months I was taking 600+ mg’s of oxy a day.
About 6 months ago I stopped the Lexapro and guess what… That coincides with my “recovery” period. Managed to get the oxy down to 400 mg’s and checked myself into detox, got on to suboxone and started counselling etc. so far so good.
Seeya
Subie


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