Tryptophan SSRIs

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

More recently, several studies in both the United States and the UK have shown that patients undergoing treatment with an SSRI will rapidly relapse when given an amino acid-containing drink that is deficient in tryptophan. The onset of the symptoms of depression is rapid (less than 24 hours) there is clinical and experimental evidence that the reduction in brain serotonin... 

Rapid relapse following administration of a tryptophan-free amino acid drink to depressed patients being treated with an SSRI... 

Add tryptophan to a standard antidepressant (usually an SSRI). There is a danger that the serotonin syndrome may occur however and occasionally the eosinophilia myalgia syndrome. The symptoms that occur with increasing severity are restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death. 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

One other important difference in the mechanism of SSRIs in OCD versus depression is that the therapeutic response in OCD may be less dependent on the immediate availability of 5HT than is the therapeutic response in depression. Thus, when tryptophan is depleted from depressed patients and 5HT synthesis is suddenly diminished, patients who have responded to SSRIs transiently deteriorate until 5HT... 

Regulation of mood, sleep, and aggression have all been shown to involve the serotoninergic system (17-19), and most antidepressant drugs currently being used inhibit 5-HT reuptake and/or act on 5-HT receptors (of which there are several subtypes). 5-HT is produced centrally from the amino acid tryptophan, and depressed mood can be induced experimentally by acute tryptophan depletion in healthy individuals. This effect is accentuated in those with a family history of depression (18-21). Similarly, depressive relapse can be initiated in individuals treated with MAO inhibitors or selective serotonin reuptake (SSRI) inhibitors by depleting tryptophan (22, 23). 

The drugs that can cause a serotonin syndrome when they are combined with SSRIs include monoamine oxidase inhibitors (including reversible inhibitors of monoamine oxidase types A and B), dextromethorphan, tryptophan, lithium, pentazocine, and carbamazepine (SEDA-17, 23) (SEDA-18, 22) (64). 

The risk of serotonin syndrome may be increased shortly after dosage increases of SSRIs or when drug interactions increase serotonin activity. Concomitant or proximal use of SSRIs, tricyclic antidepressants, or monoamine oxidase inhibitors may cause serotonin syndrome. Further, the addition of certain drugs, such as tryptophan, dextromethorphan, cocaine, or sympathomimetics, to SSRI therapy may increase the risk of developing serotonin syndrome." ... 

The symptoms of premenstrual syndrome (PMS), also called premenstrual dysphoric disorder, include depressed mood, anxiety, affective lability, and anger or irritability.79 Since low serotonin levels are thought to be involved in the etiology of depression, aggression, and impulsivity,80 specific serotonin reuptake inhibitors have been tested in PMS. The SSRI fluoxetine was found to be better than placebo.81 Since chronic treatment with SSRIs can influence many neuron systems other than serotonin,82 Steinberg et al.83 designed a study using tryptophan, relatively specific for its effect on serotonin, on the effects of symptoms of PMS. In a randomized controlled clinical trial, 37... 

Augmentation is called for when there is partial or non-response to the above approaches. Combinations of SSRIs with buspirone, clonazepam, clonidine, inositol, lithium, pindolol, olanzapine, risperidone, trazodone, tryptophan, and venlafaxine have been reported, with limited benefit. To date, only two augmenting agents have been found to be effective in double-blind studies risperidone and pindolol. Augmentation of SSRIs with clomipramine (or vice versa) is a common practice in non-responders however, this combination may lead to a substantial increase in the level of tricyclics in the blood and/or increase the risk of serotonin syndrome. Phenelzine may be helpful in symmetry-related or other atypical obsessions. Electroconvulsive therapy (ECT) should be reserved for severely depressed and suicidal OCD patients. Neurosurgery is the last resort current operations include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. The outcome of such operations is questionable. 

---